435 results on '"Eclache, Virginie"'
Search Results
152. The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11
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Lafage-Pochitaloff, Marina, Gerby, Bastien, Baccini, Véronique, Largeaud, Laetitia, Fregona, Vincent, Prade, Naïs, Juvin, Pierre-Yves, Jamrog, Laura, Bories, Pierre, Hébrard, Sylvie, Lagarde, Stéphanie, Mansat-De Mas, Véronique, Dovey, Oliver M, Yusa, Kosuke, Vassiliou, George S, Jansen, Joop H, Tekath, Tobias, Rombaut, David, Ameye, Geneviève, Barin, Carole, Bidet, Audrey, Boudjarane, John, Collonge-Rame, Marie-Agnès, Gervais, Carine, Ittel, Antoine, Lefebvre, Christine, Luquet, Isabelle, Michaux, Lucienne, Nadal, Nathalie, Poirel, Hélène A, Radford-Weiss, Isabelle, Ribourtout, Bénédicte, Richebourg, Steven, Struski, Stéphanie, Terré, Christine, Tigaud, Isabelle, Penther, Dominique, Eclache, Virginie, Fontenay, Michaela, Broccardo, Cyril, and Delabesse, Eric
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Leukemia, Myeloid, Acute ,Mice ,hemic and lymphatic diseases ,Chromosomes, Human, Pair 11 ,Myelodysplastic Syndromes ,Cell Adhesion Molecule-1 ,Animals ,Humans ,Female ,Genes, Tumor Suppressor ,Chromosome Deletion ,3. Good health - Abstract
Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis leading to peripheral cytopenias and in a substantial proportion of cases to acute myeloid leukemia. The deletion of the long arm of chromosome 11, del(11q), is a rare but recurrent clonal event in MDS. Here, we detail the largest series of 113 cases of MDS and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) harboring a del(11q) analyzed at clinical, cytological, cytogenetic, and molecular levels. Female predominance, a survival prognosis similar to other MDS, a low monocyte count, and dysmegakaryopoiesis were the specific clinical and cytological features of del(11q) MDS. In most cases, del(11q) was isolated, primary and interstitial encompassing the 11q22-23 region containing ATM, KMT2A, and CBL genes. The common deleted region at 11q23.2 is centered on an intergenic region between CADM1 (also known as Tumor Suppressor in Lung Cancer 1) and NXPE2. CADM1 was expressed in all myeloid cells analyzed in contrast to NXPE2. At the functional level, the deletion of Cadm1 in murine Lineage-Sca1+Kit+ cells modifies the lymphoid-to-myeloid ratio in bone marrow, although not altering their multilineage hematopoietic reconstitution potential after syngenic transplantation. Together with the frequent simultaneous deletions of KMT2A, ATM, and CBL and mutations of ASXL1, SF3B1, and CBL, we show that CADM1 may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies.
153. Does red blood cell size correlate with red blood cell age in mouse?
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Vaysse, Jenny, primary, Vassy, Roger, additional, Eclache, Virginie, additional, Bladier, Dominique, additional, Gattegno, Liliane, additional, and Pilardeau, Paul, additional
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- 1988
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154. Introduction pour la place de la cytogénétique dans la prise en charge des hémopathies malignes : actualisation par le Groupe francophone de cytogénétique hématologique (GFCH).
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Nguyen-Khac, Florence, Daudignon, Agnès, Eclache, Virginie, Lafage-Pochitaloff, Marina, Lefebvre, Christine, Luquet, Isabelle, and Penther, Dominique
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- 2016
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155. Genetic Characterization of B-Cell Prolymphocytic Leukemia (B-PLL): A Hierarchical Prognostic Model Involving MYCand TP53Abnormalities. on Behalf of the Groupe Francophone De Cytogenetique Hematologique(GFCH) and the French Innovative Leukemia Organization(FILO) Group
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Chapiro, Elise, Roos-Weil, Damien, Bougacha, Nadia, Gabillaud, Clementine, Dillard, Clémentine, Pramil, Elodie, Yon, Melanie, Maloum, Karim, Settegrana, Catherine, Baseggio, Lucile, Lesty, Claude, Davi, Frederic, Le Garff-Tavernier, Magali, Diop, M'boyba Khadija, Droin, Nathalie M, Dessen, Philippe, Leblond, Veronique, Algrin, Caroline, Bouzy, Simon, Eclache, Virginie, Gaillard, Baptiste, Callet-Bauchu, Evelyne, Muller, Marc, Lefebvre, Christine, Nadal, Nathalie, Ittel, Antoine, Struski, Stéphanie, Collonge-Rame, Marie-Agnes, Quilichini, Benoit, Fert-Ferrer, Sandra, Auger, Nathalie, Radford-Weiss, Isabelle, Wagner, Lena, Scheinost, Sebastian, Zenz, Thorsten, Susin, Santos, Bernard, Olivier, and Nguyen-Khac, Florence
- Abstract
B-PLL is defined by the presence of prolymphocytes in peripheral blood exceeding 55% of lymphoid cells. The diagnosis, mainly based on clinical and morphological data, can be difficult because of overlap with other B-cell malignancies. Because of the rarity of the disease, only case reports and small series describe its cytogenetic features. Few prognostic markers have been identified in this aggressive leukemia usually resistant to standard chemo-immuno therapy. We report here the cytogenetic and molecular findings in a large series of B-PLL. We also studied the in vitroresponse to novel targeted drugs on primary B-PLL cells.
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- 2018
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156. Prevalence, distribution and predictive value of XPO1 mutation in a real‐life chronic lymphocytic leukaemia cohort.
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Tueur, Giulia, Lazarian, Gregory, Eclache, Virginie, Fleury, Carole, Letestu, Rémi, Lévy, Vincent, Lefebvre, Valérie, Collon, Jean‐Francois, Zini, Jean‐Marc, Thieblemont, Catherine, Soussi, Thierry, Cymbalista, Florence, and Baran‐Marszak, Fanny
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LYMPHOCYTIC leukemia - Published
- 2020
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157. Incidence of ATRX mutations in myelodysplastic syndromes, the value of microcytosis.
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Herbaux, Charles, Duployez, Nicolas, Badens, Catherine, Poret, Nicolas, Gardin, Claude, Decamp, Mathieu, Eclache, Virginie, Daliphard, Sylvie, Murati, Anne, Cony-Makhoul, Pascale, Cheze, Stéphane, Beve, Blandine, Lacoste, Caroline, Prebet, Thomas, Hunault-Berger, Mathilde, Maloisel, Frédéric, Renneville, Aline, Figeac, Martin, Stamatoullas-Bastard, Aspasia, and Bastard, Christian
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- 2015
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158. A Retrospective Analysis of 450 TP53Mutations in a Real Life Cohort of CLL from the French Innovative Leukemia Organization (FILO) Group
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Baran-Marszak, Fanny, Vidal, Valerie, Hormi, Myriam, Eclache, Virginie, Veronese, Lauren, Tournilhac, Olivier, Davi, Frederic, Nguyen-Khac, Florence, Leblond, Veronique, Delabesse, Eric, Ysebaert, Loic, Bidet, Audrey, Dilhuydy, Marie-Sarah, Poulain, Stephanie, Herbaux, Charles, Estienne, Marie-Helene, Dartigeas, Caroline, Pastoret, Cedric, de Guibert, Sophie, Giraudier, Stephane, Dupuis, Jehan, Cornillet-Lefebvre, Pascale, Quinquenel, Anne, Laibe, Sophy, Aurran, Thérèse, Naguib, Dina, Troussard, Xavier, Sujobert, Pierre, Michallet, Anne-Sophie, Thieblemont, Catherine, Letestu, Remi, Lazarian, Gregory, Levy, Vincent, Soussi, Thierry, Raynaud, Sophie, and Cymbalista, Florence
- Abstract
In Chronic Lymphocytic Leukemia (CLL), it is well established that 17p deletions are associated with adverse prognosis and chemotherapy resistance. 17p deletions are most often associated with TP53mutations, but TP53mutations can occur in the absence of 17p deletion in about half of the cases with a similar unfavorable prognostic influence. Some patients harbor several subclones with different TP53mutations. Nonetheless, little is known on the functional effect of the various alterations and of their associations.
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- 2017
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159. Antiphospholipid syndrome during acute monocytic leukaemia.
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Mouas, Houria, Lortholary, Olivier, Eclache, Virginie, Leroux, Geneviève, Casassus, Philippe, Guillevin, Lol̈c, and Raphäel, Martine
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- 1994
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160. Incidence of AtrxMutations in Myelodysplastic Syndromes (MDS)
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Herbaux, Charles, Duployez, Nicolas, Badens, Catherine, Poret, Nicolas, Gardin, Claude, Eclache, Virginie, Daliphard, Sylvie, Murati, Anne, Cony-Makhoul, Pascale, Cheze, Stephane, Beve, Blandine, Prebet, Thomas, Hunault-Berger, Mathilde, Renneville, Aline, Figeac, Martin, Stamatoullas, Aspasia, Bastard, Christian, Fenaux, Pierre, Preudhomme, Claude, and Rose, Christian
- Abstract
INTRODUCTION
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- 2014
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161. Occurrence of myelodysplastic syndrome in 2 patients with reticular dysgenesis.
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Lagresle-Peyrou, Chantal, Neven, Bénédicte, Six, Emmanuelle, Picard, Capucine, Demerens-de Chappedelaine, Corinne, Bertrand, Yves, Jabado, Nada, Chomienne, Christine, Radford-Weiss, Isabelle, Brouzes, Chantal, Asnafi, Vahid, MacIntyre, Elizabeth, Donadieu, Jean, Beaupain, Blandine, Fenaux, Pierre, Eclache, Virginie, Fischer, Alain, and Cavazzana-Calvo, Marina
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- 2011
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162. Incidence and Prognostic Value of TP53Mutations in Lower Risk MDS with Del 5q.
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Bally, Cecile, Ades, Lionel, Renneville, Aline, Raynaud, Sophie, Eclache, Virginie, Cluzeau, Thomas, Hunault-Berger, Mathilde, Stamatoullas, Aspasia, Bastard, Christian, Fontenay, Michaela, Mozziconacci, Marie-Joelle, Preudhomme, Claude, de The, Hugues, Fenaux, Pierre, and Lehmann-Che, Jacqueline
- Abstract
Abstract 2809
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- 2012
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163. Deletion of the Tumor Suppressor Gene NF1Is Found In 3.5% of 485 De NovoAdult Myeloid Leukemia and Is Correlated with Unfavourable Cytogenetic: On Behalf of the ALFA Group
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Labis, Elise, Roche-Lestienne, Catherine, Nibourel, Olivier, Boissel, Nicolas, Roumier, Christophe, Terre, Christine, Perot, Christine, Eclache, Virginie, Gachard, Nathalie, Tigaud, Isabelle, Plessis, Ghislaine, Cuccuini, Wendy, Geffroy, Sandrine, Helevaut, Nathalie, Quief, Sabine, Figeac, Martin, Renneville, Aline, Cheok, Meyling, Quesnel, Bruno, Dombret, Herve, and Preudhomme, Claude
- Abstract
Abstract 4171
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- 2010
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164. Specific Chromosomal IGTranslocations Have Different Prognosis In Chronic Lymphocytic Leukemia
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Nguyen-Khac, Florence, Lesty, CLaude, Chapiro, Elise, Grelier, Aurore, Luquet, Isabelle, Radford-Weiss, Isabelle, Fertferrer, Sandra, Callet-Bauchu, Evelyne, Lefebvre, Christine, Lippert, Eric, Terré, Christine, Michaux, Lucienne, Collonge-Rame, Marie-Agnes, Barin, Carole, Mugneret, Francine, Talmant, Pascaline, Taviaux, Sylvie, Struski, Stephanie, Eclache, Virginie, Gervais, Carine, Quilichini, Benoit, Gachard, Nathalie, Richebourg, Steven, Dastugue, Nicole, Settegrana, Catherine, Davi, Frederic, Maloum, Karim, and Merle-Beral, Helene
- Abstract
Abstract 582
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- 2010
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165. Chromosomal Abnormalities in Transformed Ph-Negative Myeloproliferative Neoplasm Are Independent of the JAK2and the TET2Statuses.
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Nguyen-Khac, Florence, Couronne, Lucile, Eclache, Virginie, Andrieux, Joris, Lippert, Eric, Kosmider, Olivier, Mugneret, Francine, Collonge-Rame, Marie-Agnes, Penther, Dominique, Lafage, Marina, Gachard, Nathalie, Nadal, Nathalie, Mozziconacci, Marie-Joelle, Dastugue, Nicole, Bilhou-Nabera, Chrystele, Struski, Stephanie, Cabrol, Christine, Radford-Weiss, Isabelle, Lesty, Claude, and Bernard, Olivier A
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Abstract 2900
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- 2009
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166. Are myelodysplastic syndromes and acute myeloid leukaemia occurring during the course of lymphoma always therapy related?
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Bigenwald, Camille, Harel, Stéphanie, Chevignon, Florian, Roos‐Weil, Damien, Bernard, Olivier A., Amorim, Sandy, Brice, Pauline, Adès, Lionel, Nloga, Anne Marie, Sébert, Marie, Braun, Thorsten, Eclache, Virginie, Thieblemont, Catherine, and Fenaux, Pierre
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MYELODYSPLASTIC syndromes , *MYELODYSPLASTIC syndromes treatment , *LEUKEMIA treatment , *LYMPHOMA treatment , *CHEMOTHERAPY complications , *RADIOTHERAPY complications - Abstract
The article discusses a study which examined the clinical and biological characteristics of patients with both myelodysplastic syndromes/acute myeloid leukaemia (MDS/AML) and lymphoma. Topics include the complications of cytotoxic chemotherapy (CT) and radiotherapy (RT), the occurrence of MDS/AML in patients with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL), and the diagnosis of MDS/AML.
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- 2018
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167. Impact of baseline cytogenetic findings and cytogenetic response on outcome of high-risk myelodysplastic syndromes and low blast count AML treated with azacitidine.
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Sébert, Marie, Komrokji, Rami S, Sekeres, Mikkael A., Prebet, Thomas, Cluzeau, Thomas, Santini, Valeria, Gyan, Emmanuel, Sanna, Alessandro, Ali, Najla HAl, Hobson, Sean, Eclache, Virginie, List, Alan, Fenaux, Pierre, and Adès, Lionel
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ACUTE myeloid leukemia treatment , *MYELODYSPLASTIC syndromes treatment , *AZACITIDINE , *CYTOGENETICS , *HEMATOLOGY , *THERAPEUTICS - Abstract
Karyotype according to the revised IPSS is a strong independent prognostic factor for overall survival (OS) in myelodysplastic syndromes (MDS), however established in untreated patients. The prognostic impact of cytogenetics and cytogenetic response (CyR) in MDS patients receiving azacitidine (AZA) remains uncertain. We examined the prognostic value of baseline cytogenetics and CyR for overall response rate (ORR) and OS in 702 AZA-treated higher risk MDS and low blast count acute myeloid leukemia (AML), including 493 (70%) with abnormal karyotype. None of the cytogenetic abnormalities had significant impact on ORR (43.9%) or complete response (15.35%), except 3q abnormalities and complex karyotypes, which were associated with a lower ORR. OS differed significantly across all R-IPSS cytogenetic subgroups (p < 10 −4 ) but patients with non complex del(7q) had similar survival as patients with normal cytogenetics. CyR was achieved in 32% of the 281 evaluable patients with abnormal cytogenetics, was complete (CCyR) in 71 (25.3%) patients. We found no correlation between hematological response and cytogenetic response and 21% of the patients with CCyR did not achieve morphological response. In the 281 patients, we found no impact of CyR on survival, but when restricting to MDS (ie: <20% marrow blasts) achievement of CCyR was associated with better OS. [ABSTRACT FROM AUTHOR]
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- 2017
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168. Impact of cytogenetic abnormalities in adults with Ph-negative B-cell precursor acute lymphoblastic leukemia.
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Lafage-Pochitaloff, Marina, Baranger, Laurence, Hunault, Mathilde, Cuccuini, Wendy, Lefebvre, Christine, Bidet, Audrey, Tigaud, Isabelle, Eclache, Virginie, Delabesse, Eric, Bilhou-Nabéra, Chrystèle, Terré, Christine, Chapiro, Elise, Gachard, Nathalie, Mozziconacci, Marie-Joelle, Ameye, Geneviève, Porter, Sarah, Grardel, Nathalie, Béné, Marie C., Chalandon, Yves, and Graux, Carlos
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B cells , *LYMPHOBLASTIC leukemia , *LYMPHOBLASTIC leukemia treatment , *LYMPHOBLASTIC leukemia prognosis , *CYTOGENETICS , *PATIENTS - Abstract
Multiple cytogenetic subgroups have been described in adult Philadelphia chromosome (Ph)-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), often comprising small numbers of patients. In this study, we aimed to reassess the prognostic value of cytogenetic abnormalities in a large series of 617 adult patients with Ph-negative BCP-ALL (median age, 38 years), treated in the intensified Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/2005 trials. Combined data from karyotype, DNA index, fluorescence in situ hybridization and polymerase chain reaction screening for relevant abnormalities were centrally reviewed and were informative in 542 cases (88%), allowing classification in 10 exclusive primary cytogenetic subgroups and in secondary subgroups, including complex andmonosomal karyotypes. Prognostic analyses focused on cumulative incidence of failure (including primary refractoriness and relapse), event-free survival, and overall survival. Only 2 subgroups, namely t(4;11)/ KMT2A-AFF1 and 14q32/IGH translocations, displayed a significantly worse outcome in this context, still observed after adjustment for age and after censoring patients who received allogeneic stem cell transplantation (SCT) in first remission at SCTtime.Aworse outcome was also observed in patients with low hypodiploidy/near triploidy, but this was likely related to their higher age and worse tolerance to therapy. The other cytogenetic abnormalities, including complex andmonosomal karyotypes, had no prognostic value in these intensive protocols designed for adult patients up to the age of 60 years. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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169. Prognostic value of TP53 gene mutations in myelodysplastic syndromes and acute myeloid leukemia treated with azacitidine.
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Bally, Cecile, Adès, Lionel, Renneville, Aline, Sebert, Marie, Eclache, Virginie, Preudhomme, Claude, Mozziconacci, Marie-Joelle, de The, Hugues, Lehmann-Che, Jacqueline, and Fenaux, Pierre
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MYELODYSPLASTIC syndromes treatment , *P53 protein , *GENETIC mutation , *ACUTE myeloid leukemia treatment , *AZACITIDINE , *KARYOTYPES , *CANCER prognosis , *THERAPEUTICS - Abstract
Abstract: TP53 mutations are found in 5–10% of MDS and AML, where they are generally associated with complex karyotype and an overall poor prognosis. However, the impact of TP53 mutations in MDS treated with azacitidine (AZA) remains unclear. We analyzed TP53 mutations in 62 patients with high risk MDS or AML treated with AZA. A TP53 mutation was found in 23 patients (37.1%), associated with complex karyotype in 18 (78.3%) of them. TP53 mutations had no significant impact on response or complete response to AZA (p =0.60 and p =0.26, respectively). By univariate analysis, OS was negatively influenced by the presence of TP53 mutation (median OS 12.4 months versus 23.7 months, p <10−4), abnormal cytogenetics (median OS 14.4 months vs 33 months, p =0.02) complex cytogenetics (median OS 12.7 months versus 23.7 months, p =0.0005), and a diagnosis of AML (median 14.5 months vs 21.2 months for MDS or CMML, p =0.02). By multivariate analysis, only TP53 mutational status (HR 2.89 (95% confidence interval 1.38–6.04; p =0.005) retained statistical significance for OS. Results were similar when the analysis was restricted to MDS and CMML patients, excluding AML (HR=2.46 (95% confidence interval: 1.1–6.4); p =0.04)). Thus, TP53 mutations strongly correlated with poorer survival in higher risk MDS and AML treated with AZA. [Copyright &y& Elsevier]
- Published
- 2014
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170. The degree of BCR and NFAT activation predicts clinical outcomes in chronic lymphocytic leukemia.
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Le Roy, Christine, Deglesne, Pierre-Antoine, Chevallier, Natlialie, Beitar, Taoufik, Eclache, Virginie, Quettier, Maude, Boubaya, Marouane, Letestu, Rémi, Lévy, Vincent, Ajchenbaum-Cymbalista, Florence, and Varin-Blank, Nadine
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B cell receptors , *CHRONIC lymphocytic leukemia , *CELLULAR signal transduction , *HEALTH outcome assessment , *PHOSPHORYLATION , *IMMUNOGLOBULIN M , *INTRACELLULAR calcium - Abstract
B-cell antigen receptor (BCR)-mediated signaling plays a critical role in chronic lymphocytic leukemia (CLL) pathogenesis and gives an in vitro survival advantage to B cells isolated from patients with unfavorable prognostic factors. In this study, we undertook to elucidate the signaling intermediates responsible for this biologic alteration. In responding cells only, In vitro BCR engagement triggers global phosphorylation of Syk, activation of phosphollpase C&lgr;2, and intracellular calcium mobilization, reflecting competency of BCR signaling. The calclumcalcineurin-dependent transcription factor NFAT2 is up-regulated and to some extent constitutively activated in all CLLB cells. In contrast, its DNA-binding capacity is enhanced on IgM stimulation In responding cells only. NFAT inhibition using the VIVIT peptide prevents Induction of CD23 target gene and IgM-induced survival, converting responding cells to unresponsive status. At the opposite, ionomycin-induced NFAT activity allows survival of nonresponding cells. These results demonstrate that the functional heterogeneity relies on variability of protein levels establishing BCR-dependent thresholds and NFAT-dependent activation. Finally, status of the BCR-NFAT pathway for each patient reveals its relevance for CLL clinical outcome and points out to BCR-NFAT Intermediates as promising functional therapeutic targets. [ABSTRACT FROM AUTHOR]
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- 2012
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171. Will a peripheral blood (PB) sample yield the same diagnostic and prognostic cytogenetic data as the concomitant bone marrow (BM) in myelodysplasia?
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Cherry, Athena M., Slovak, Marilyn L., Campbell, Lynda J., Chun, Kathy, Eclache, Virginie, Haase, Detlef, Haferlach, Claudia, Hildebrandt, Barbara, Iqbal, Anwar M., Jhanwar, Suresh C., Ohyashiki, Kazuma, Sole, Francesc, Vandenberghe, Peter, VanDyke, Daniel L., Zhang, Yanming, and Dewald, Gordon W.
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MYELODYSPLASTIC syndromes , *CYTOGENETICS , *BONE marrow , *DYSPLASIA , *CHROMOSOME abnormalities , *KARYOTYPES , *BLOOD testing - Abstract
Abstract: In patients with myelodysplastic syndromes (MDS), chromosome anomalies are detected by conventional cytogenetic studies (CCS) and/or interphase fluorescence in situ hybridization (FISH) of bone marrow (BM) samples and provide prognostic and diagnostic information, which can direct therapy. Whether peripheral blood (PB) can be substituted for bone marrow in these cases and can provide the same information remains unknown. Concurrent BM and PB specimens collected from 100 patients with recently diagnosed MDS were studied using both CCS and FISH. While 68% of BM samples showed an abnormal karyotype by CCS, only 31% of PB samples were abnormal by CCS. In 12% of patients, FISH and CCS were discordant due to the inability of the FISH panel to detect all possible abnormalities. However, only one case (1%) had a cryptic abnormality detected by FISH. BM and PB FISH were discordant in 3% of cases, most likely due to the smaller clone size in PB vs. BM. While PB should not be substituted for BM at diagnosis, it is a viable alternative for monitoring patients using the appropriate FISH probe(s). [Copyright &y& Elsevier]
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- 2012
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172. Chronic lymphocytic leukemia and prolymphocytic leukemia with MYC translocations: a subgroup with an aggressive disease course.
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Put, Natalie, Roosbroeck, Katrien, Konings, Peter, Meeus, Peter, Brusselmans, Caroline, Rack, Katrina, Gervais, Carine, Nguyen-Khac, Florence, Chapiro, Elise, Radford-Weiss, Isabelle, Struski, Stéphanie, Dastugue, Nicole, Gachard, Nathalie, Lefebvre, Christine, Barin, Carole, Eclache, Virginie, Fert-Ferrer, Sandra, Laibe, Sophy, Mozziconacci, Marie-Joëlle, and Quilichini, Benoît
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CHRONIC lymphocytic leukemia , *CHRONIC diseases , *PUBLIC health , *CANCER , *IMMUNOPHARMACOLOGY - Abstract
Translocations involving MYC are rare in chronic lymphocytic leukemia (CLL), and up to now, their prognostic significance remains unclear. We report the characteristics of 21 patients with CLL and nine patients with prolymphocytic leukemia (PLL), diagnosed in multiple centers ( n = 13), which showed an MYC translocation demonstrated by fluorescence in situ hybridization. The prevalence was estimated to be <1%. Advanced age and male predominance were observed. Morphological analysis frequently revealed the presence of prolymphocytes. A typical 'CLL-immunophenotype' was found in four of nine cases with PLL. Moreover, CD5 and CD23 were frequently expressed in PLL. The latter findings are atypical for PLL and may suggest transformation or progression of an underlying CLL. MYC translocations were frequently observed with concomitant adverse cytogenetic markers, such as del(11q) ( n = 8/30) and/or del(17p)/monosomy 17 ( n = 7/30). In addition, the presence of unbalanced translocations ( n = 24 in 13/30 cases) and complex karyotype ( n = 16/30) were frequent in cases with MYC translocations. Altogether, del(17p)/monosomy 17, del(11q), and/or complex karyotype were observed in 22 of 30 patients. Survival outcome was poor: the median time to treatment was only 5 months, and overall survival (OS) from clinical diagnosis and from genetic detection was 71 and 19 months, respectively. In conclusion, CLL/PLL with MYC translocations is a rare entity, which seems to be associated with adverse prognostic features and unfavorable outcome. [ABSTRACT FROM AUTHOR]
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- 2012
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173. Treatment by Lenalidomide in lower risk myelodysplastic syndrome with 5q deletion—The GFM experience
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Le Bras, Fabien, Sebert, Marie, Kelaidi, Charikleia, Lamy, Thierry, Dreyfus, François, Delaunay, Jacques, Banos, Anne, Blanc, Michel, Vey, Norbert, Schmidt, Aline, Visanica, Sorin, Eclache, Virginie, Turlure, Pascal, Beyne-Rauzy, Odile, Guerci, Agnès, Delmer, Alain, de Botton, Stéphane, Rea, Delphine, Fenaux, Pierre, and Adès, Lionel
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MYELODYSPLASTIC syndromes treatment , *THALIDOMIDE , *RED blood cell transfusion , *BLOOD cell count , *NEUTROPENIA , *THROMBOCYTOPENIA , *CHROMOSOME abnormalities - Abstract
Abstract: We treated 95 RBC transfusion dependent lower risk MDS with del 5q with Lenalidomide (10mg/day, 3 weeks/4 weeks). Median age was 70.4, median interval from diagnosis 29 months. IPSS was low in 31% and intermediate-1 in 69% patients. Del 5q was isolated, with 1 additional and >1 additional abnormality in 79%, 14%, and 6% patients, respectively. 62 (65%) patients achieved transfusion independence (TI). The only significant factor predicting TI was baseline platelet count >150G/L and platelet decrease by at least 50% during the first weeks of treatment (p =0.001). Grade III–IV neutropenia and thrombocytopenia were seen in 74% and 37.9% of the cases, respectively, and 3 deaths were attributed to cytopenias. Eight (8%) patients developed deep venous thrombosis (DVT). Platelet decrease by less than 50% predicted a higher risk of DVT. Only 6 patients (6.3%) patients progressed to AML, but median follow-up time was short (18 months). We confirm the high rate of TI with Lenalidomide in lower risk MDS with del 5q. Very close patient monitoring for cytopenias and DVT is mandatory, especially during the first weeks of treatment. [Copyright &y& Elsevier]
- Published
- 2011
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174. Characteristics and outcome of myelodysplastic syndromes (MDS) with isolated 20q deletion: A report on 62 cases
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Braun, Thorsten, de Botton, Stéphane, Taksin, Anne-Laure, Park, Sophie, Beyne-Rauzy, Odile, Coiteux, Valérie, Sapena, Rosa, Lazareth, Anne, Leroux, Geneviève, Guenda, Khaled, Cassinat, Bruno, Fontenay, Michaela, Vey, Norbert, Guerci, Agnès, Dreyfus, François, Bordessoule, Dominique, Stamatoullas, Aspasia, Castaigne, Sylvie, Terré, Christine, and Eclache, Virginie
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MYELODYSPLASTIC syndromes , *CHROMOSOME abnormalities , *RETICULOCYTES , *CYTOGENETICS , *CONFIDENCE intervals , *APLASTIC anemia , *ACUTE myeloid leukemia , *THROMBOCYTOPENIA , *GENETICS - Abstract
Abstract: Isolated 20q deletion is common in MDS and considered of good prognosis, but no large series have been reported. We compared characteristics of 62 MDS patients with isolated del 20q, 36 patients with del 20q and other cytogenetic abnormalities, and 1335 MDS patients without del20q. Significant differences between MDS with isolated del 20q and patients without del 20q were lower platelet count (mean 144 vs. 196 G/l, p =0.005), lower marrow blast count (mean 3.9% vs. 5.6%, p =0.0008), and higher reticulocyte count (mean 72.5 vs. 51.7 G/l, p =0.04). Ten (16%) patients with isolated del 20q had Hb>12g/dl and platelets <100 G/l, compared to 7.3% of patients without del 20q (p =0.025). Review of marrow slides of those 10 patients showed that could be readily identified as MDS prior to cytogenetics. Fourteen percent of patients with isolated del 20q progressed to AML compared to 11% with one and 24% with several additional abnormalities. Median survival was 54 months in patients with isolated del 20q, not reached and 12 months for del 20q with one and several additional abnormalities, respectively (p =0.035) confirming the favorable prognosis of del 20q without complex abnormalities. [Copyright &y& Elsevier]
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- 2011
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175. Detection of chromosomal abnormalities associated with chronic lymphocytic leukemia: what is the best method?
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el-Taweel, Maha, Barin, Carole, Cymbalista, Florence, and Eclache, Virginie
- Subjects
- *
CHROMOSOME abnormalities , *CHRONIC lymphocytic leukemia , *B cell lymphoma , *BIOMARKERS , *HEALTH outcome assessment , *CYTOGENETICS , *DIAGNOSTIC use of fluorescence in situ hybridization , *CANCER prognosis , *GENETICS - Abstract
Abstract: B-cell chronic lymphocytic leukemia (CLL) follows a heterogeneous clinical course, for which several biological markers may predict clinical outcome. Cytogenetic aberrations are considered major prognostic indicators for predicting the survival of CLL patients. Given the difficulties in obtaining abnormal metaphases in CLL, fluorescent in situ hybridization (FISH) with specific probes is generally used to detect the most frequent abnormalities. To determine the best strategy for identifying cytogenetic abnormalities, we compared results obtained by FISH analysis on peripheral blood mononuclear cells with those obtained by FISH after culture with mitogens. We studied 46 CLL patients selected from two different institutions. The most frequent structural aberrations leading to loss of genetic material were loss of the 13q14 region, in 32 cases (70%), and loss of TP53 in 11 cases (24%). Of the 46 cases patients, 10 patients (21.7%) had deletion of the ATM locus at 11q22 and 8 patients (17%) had trisomy 12. Results could be interpreted as discordant in four cases in which the abnormal clone was small and both values were around the threshold. FISH performed on stimulated cells detected the same frequency of abnormalities as FISH performed without culture. This equivalence between the two techniques allows performing both conventional cytogenetic and FISH analyses on the same sample. [Copyright &y& Elsevier]
- Published
- 2009
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176. Clinical and biological features associated with taste loss in internal medicine patients. A cross-sectional study of 100 cases
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Kettaneh, Adrien, Pariès, Jacques, Stirnemann, Jérôme, Steichen, Olivier, Eclache, Virginie, Fain, Olivier, and Thomas, Michel
- Subjects
- *
PATIENTS , *ALCOHOL , *TOBACCO , *MEDICINE - Abstract
Abstract: Which are the main features associated with taste loss in patients exposed to a wide range of drugs and diseases? In 100 consecutive patients admitted to a ward of internal medicine, we assessed taste complaints, performance status, alcohol and tobacco consumptions, diseases, drugs and laboratory data, measuring the electrical taste threshold as primary outcome. After adjusting for age, taste thresholds were not associated with sex, body mass index, tobacco, thrush, drugs, aliageusia and phantogeusia. Features associated with threshold increase included alcohol intake ≥10gd−1, impaired performance status, complaint of taste loss, atrophic glossitis, cerebral disease, and an erythrocyte mean corpuscular volume. A multivariate analysis identified age, alcohol intake, complaint of loss or altered taste, mean corpuscular volume, and performance status as independent factors associated with taste loss. Inpatients may be screened for taste loss by a few features, to identify those for whom a nutritional intervention should be focused. [Copyright &y& Elsevier]
- Published
- 2005
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177. Treatment of adult systemic mastocytosis with interferon-α: results of a multicentre phase II trial on 20 patients.
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Casassus, Philippe, Caillat-Vigneron, Nadine, Martin, Antoine, Simon, Jeanne, Gallais, Valérie, Beaudry, Patrice, Eclache, Virginie, Laroche, Liliane, Lortholary, Pierre, Raphaël, Martine, Guillevin, Loïc, and Lortholary, Olivier
- Subjects
- *
MAST cell disease , *INTERFERONS , *CLINICAL trials - Abstract
Summary. Systemic mastocytosis (SM) is characterized by proliferation of mast cells in various organs, which may release a wide variety of mediators, thereby explaining the broad clinical spectrum of disease manifestations. The potentially life-threatening systemic symptoms and tumoral proliferation are poorly controlled despite the use of several cytotoxic chemotherapies and/or symptomatic treatments. Twenty consecutive adult SM patients with histologically confirmed bone marrow (BM) involvement received interferon-α subcutaneously (1–5 million units/m2 /d, with progressive dose intensification over the first month of treatment) and were evaluated after 6 months of therapy. Seven of them had previously received symptomatic treatments, including steroids, which were ineffective. Among the 13 patients treated for at least 6 months, seven partial and six minor responses, mainly concerning vascular congestion and skin lesions, were obtained, while BM infiltration remained unchanged in 12 patients. The significant reduction of mast-cell mediator levels after 6 months of treatment was not predictive of clinical remission. The rate of depression was unexpectedly high (seven patients; 35%). Two patients died soon after starting therapy (one myocardial infarction, one septic shock). Six months of interferon-α may relieve vascular congestion in adults with SM, probably by inhibiting mast-cell degranulation. [ABSTRACT FROM AUTHOR]
- Published
- 2002
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178. Molecular landscape of mature B-cell lymphoproliferative disorders with BCL3-translocation: A Groupe Francophone de Cytogénétique Hématologique (GFCH)/French Innovative Leukemia Organization (FILO) study.
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Véronèse L, Bensaber H, Dannus LT, Giannone G, Choiset C, Grimpret C, Abermil N, Balducci E, Bidet A, Chapiro E, Couronné L, Daudignon A, Douet-Gilbert N, Eclache V, Gaillard B, Gaillard JB, Hsoumi F, Lefebvre C, Nadal N, Mozziconacci MJ, Penther D, Ribourtout B, Richebourg S, Rigollet L, Terre C, Soler G, Tournilhac O, Guièze R, Nguyen-Khac F, and Tchirkov A
- Subjects
- Humans, Male, Female, Middle Aged, Lymphoproliferative Disorders genetics, Lymphoproliferative Disorders diagnosis, Aged, B-Lymphocytes metabolism, B-Lymphocytes pathology, Adult, France, B-Cell Lymphoma 3 Protein, Translocation, Genetic
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- 2024
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179. Clinical and biological characterization of involvement of nasal-associated lymphoid tissues in chronic lymphocytic leukemia.
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Ranaweera Arachchige T, Mendiburu C, Martin A, Fleury C, Dondi E, Letestu R, Eclache V, Baran-Marszak F, Cymbalista F, and Lazarian G
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- Humans, Male, Aged, Female, Middle Aged, Lymphoid Tissue pathology, Aged, 80 and over, Leukemia, Lymphocytic, Chronic, B-Cell pathology
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- 2024
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180. Retrospective analysis of a cohort of 41 de novo B-cell prolymphocytic leukemia patients: impact of genetics and targeted therapies (a FILO study).
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Algrin C, Pérol L, Chapiro E, Baseggio L, Maloum K, Settegrana C, Lesesve JF, Siavellis J, Delmer A, Michallet AS, Ferrant E, Feugier P, Tomowiak C, Brion A, Ghez D, Fornecker LM, Ivanoff S, Struski S, Sutton L, Radford-Weiss I, Eclache V, Lefebvre C, Leblond V, Nguyen-Khac F, and Roos-Weil D
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- Humans, Retrospective Studies, Leukemia, Prolymphocytic, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell
- Published
- 2023
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181. The presence of a chromosomal abnormality in cytopenia without dysplasia identifies a category of high-risk clonal cytopenia of unknown significance.
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Brett VE, Lechevalier N, Trimoreau F, Dussiau C, Dimicoli-Salazar S, Coster L, Luquet I, Nadal N, Ribourtout B, Chapiro E, Lefebvre C, Tondeur S, Balducci E, Nguyen-Khac F, Borie C, Radford-Weiss I, Barin C, Eclache V, Mansier O, and Bidet A
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- Humans, Chromosome Aberrations, Mutation, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes pathology, Hematologic Neoplasms, Chromosome Disorders, Anemia
- Abstract
Myelodysplastic syndromes (MDS) are hematological malignancies classically defined by the presence of cytopenia(s) and dysmorphic myeloid cells. It is now known that MDS can be preceded by a pre-malignant condition called clonal cytopenia of unknown significance (CCUS), which associates a clonality marker with cytopenia in the absence of criteria of dysplasia. However, to date, it is not clear whether chromosomal abnormalities should be considered in the definition of CCUS or if they carry a prognostic impact in CCUS patients. In this study, we analyzed the clinico-biological features and outcomes of 34 patients who presented with one or more cytopenias, an absence of significant dysplasia, and a presence of a chromosomal abnormality (CA). We named this entity chromosomal abnormality with cytopenia of undetermined significance (CACtUS). We show that these patients are slightly older than MDS patients and that they more frequently presented with normocytic anemia. Most CACtUS patients exhibited only one unbalanced CA. The number and type of mutations were comparable between CACtUS patients and MDS patients. Regardless of the cytogenetic abnormality, the clinicobiological characteristics, overall survival, and risk of progression to high-risk (HR) MDS were similar between CACtUS patients and low-risk MDS patients. Thus, we suggest that CACtUS patients can be considered as HR-CCUS and should receive the follow-up regimen recommended for MDS patients., (© 2022 Wiley Periodicals LLC.)
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- 2023
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182. TP53 mutations at codon 234 are associated with chlorambucil treatment in chronic lymphocytic leukemia.
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Lazarian G, Theves F, Hormi M, Letestu R, Eclache V, Bidet A, Cornillet-Lefebvre P, Davi F, Delabesse E, Estienne MH, Etancelin P, Kosmider O, Laibe S, Lode L, Muller M, Nadal N, Naguib D, Pastoret C, Poulain S, Sujobert P, Veronese L, Imache S, Lefebvre V, Cymbalista F, Baran-Marszak F, and Soussi T
- Subjects
- Codon, Humans, Mutation, Chlorambucil therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Tumor Suppressor Protein p53 genetics
- Published
- 2022
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183. The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11.
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Lafage-Pochitaloff M, Gerby B, Baccini V, Largeaud L, Fregona V, Prade N, Juvin PY, Jamrog L, Bories P, Hébrard S, Lagarde S, Mansat-De Mas V, Dovey OM, Yusa K, Vassiliou GS, Jansen JH, Tekath T, Rombaut D, Ameye G, Barin C, Bidet A, Boudjarane J, Collonge-Rame MA, Gervais C, Ittel A, Lefebvre C, Luquet I, Michaux L, Nadal N, Poirel HA, Radford-Weiss I, Ribourtout B, Richebourg S, Struski S, Terré C, Tigaud I, Penther D, Eclache V, Fontenay M, Broccardo C, and Delabesse E
- Subjects
- Animals, Cell Adhesion Molecule-1 genetics, Chromosome Deletion, Chromosomes, Human, Pair 11, Female, Genes, Tumor Suppressor, Humans, Mice, Cell Adhesion Molecule-1 metabolism, Leukemia, Myeloid, Acute genetics, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes pathology
- Abstract
Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis leading to peripheral cytopenias and in a substantial proportion of cases to acute myeloid leukemia. The deletion of the long arm of chromosome 11, del(11q), is a rare but recurrent clonal event in MDS. Here, we detail the largest series of 113 cases of MDS and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) harboring a del(11q) analyzed at clinical, cytological, cytogenetic, and molecular levels. Female predominance, a survival prognosis similar to other MDS, a low monocyte count, and dysmegakaryopoiesis were the specific clinical and cytological features of del(11q) MDS. In most cases, del(11q) was isolated, primary and interstitial encompassing the 11q22-23 region containing ATM, KMT2A, and CBL genes. The common deleted region at 11q23.2 is centered on an intergenic region between CADM1 (also known as Tumor Suppressor in Lung Cancer 1) and NXPE2. CADM1 was expressed in all myeloid cells analyzed in contrast to NXPE2. At the functional level, the deletion of Cadm1 in murine Lineage-Sca1+Kit+ cells modifies the lymphoid-to-myeloid ratio in bone marrow, although not altering their multilineage hematopoietic reconstitution potential after syngenic transplantation. Together with the frequent simultaneous deletions of KMT2A, ATM, and CBL and mutations of ASXL1, SF3B1, and CBL, we show that CADM1 may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2022
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184. Clinical and biological characteristics of leukemia cutis in chronic lymphocytic leukemia: A study of the French innovative leukemia organization (FILO).
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Lazarian G, Munger M, Quinquenel A, Dilhuydy MS, Veronese L, Luque Paz D, Guièze R, Ledoux-Pilon A, Paillassa J, Merabet F, Vial JP, Bidet A, Waultier Rascalou A, Broseus J, Roos-Weil D, Lavaud A, Molina L, Laribi K, Hivert B, Friedrich C, Carpentier B, Ysebaert L, Van Den Neste E, Willems L, Corby A, Poulain S, Eclache V, Maubec E, Martin A, Feugier P, Delmer A, Baran-Marszak F, Leprêtre S, and Cymbalista F
- Subjects
- Adult, Aged, Aged, 80 and over, B-Lymphocytes pathology, Female, France epidemiology, Humans, Leukemia, Lymphocytic, Chronic, B-Cell epidemiology, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Male, Middle Aged, Mutation, Skin Neoplasms epidemiology, Skin Neoplasms genetics, Treatment Outcome, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Skin pathology, Skin Neoplasms pathology
- Published
- 2021
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185. Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53.
- Author
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Chapiro E, Pramil E, Diop M, Roos-Weil D, Dillard C, Gabillaud C, Maloum K, Settegrana C, Baseggio L, Lesesve JF, Yon M, Jondreville L, Lesty C, Davi F, Le Garff-Tavernier M, Droin N, Dessen P, Algrin C, Leblond V, Gabarre J, Bouzy S, Eclache V, Gaillard B, Callet-Bauchu E, Muller M, Lefebvre C, Nadal N, Ittel A, Struski S, Collonge-Rame MA, Quilichini B, Fert-Ferrer S, Auger N, Radford-Weiss I, Wagner L, Scheinost S, Zenz T, Susin SA, Bernard OA, and Nguyen-Khac F
- Subjects
- Aged, Aged, 80 and over, Chromosome Aberrations, Cytogenetic Analysis, Female, Humans, Male, Middle Aged, Prognosis, Leukemia, Prolymphocytic, B-Cell genetics, Proto-Oncogene Proteins c-myc genetics, Tumor Suppressor Protein p53 genetics
- Abstract
B-cell prolymphocytic leukemia (B-PLL) is a rare hematological disorder whose underlying oncogenic mechanisms are poorly understood. Our cytogenetic and molecular assessments of 34 patients with B-PLL revealed several disease-specific features and potential therapeutic targets. The karyotype was complex (≥3 abnormalities) in 73% of the patients and highly complex (≥5 abnormalities) in 45%. The most frequent chromosomal aberrations were translocations involving MYC [t(MYC)] (62%), deletion (del)17p (38%), trisomy (tri)18 (30%), del13q (29%), tri3 (24%), tri12 (24%), and del8p (23%). Twenty-six (76%) of the 34 patients exhibited an MYC aberration, resulting from mutually exclusive translocations or gains. Whole-exome sequencing revealed frequent mutations in TP53, MYD88, BCOR, MYC, SF3B1, SETD2, CHD2, CXCR4, and BCLAF1. The majority of B-PLL used the IGHV3 or IGHV4 subgroups (89%) and displayed significantly mutated IGHV genes (79%). We identified 3 distinct cytogenetic risk groups: low risk (no MYC aberration), intermediate risk (MYC aberration but no del17p), and high risk (MYC aberration and del17p) (P = .0006). In vitro drug response profiling revealed that the combination of a B-cell receptor or BCL2 inhibitor with OTX015 (a bromodomain and extra-terminal motif inhibitor targeting MYC) was associated with significantly lower viability of B-PLL cells harboring a t(MYC). We concluded that cytogenetic analysis is a useful diagnostic and prognostic tool in B-PLL. Targeting MYC may be a useful treatment option in this disease., (© 2019 by The American Society of Hematology.)
- Published
- 2019
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186. Isolated isochromosomes i(X)(p10) and idic(X)(q13) are associated with myeloid malignancies and dysplastic features.
- Author
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Penther D, Etancelin P, Lusina D, Bidet A, Quilichini B, Gaillard B, Rafdord-Weiss I, Mozziconacci MJ, Ittel A, Roche-Lestienne C, Barin C, Soler G, Daudignon A, Nadal N, Chapiro E, Lefebvre C, Godon C, Nadeau G, Mugneret F, Richebourg S, Viailly PJ, Ferret Y, Nguyen-Khac F, and Eclache V
- Subjects
- Age Distribution, Aged, Bone Marrow pathology, Chromosomes, Human, X ultrastructure, DNA-Binding Proteins genetics, Dioxygenases, Female, Follow-Up Studies, Genes, Neoplasm, Humans, Leukemia, Myeloid epidemiology, Leukemia, Myeloid pathology, Male, Middle Aged, Mutation, Myelodysplastic Syndromes epidemiology, Myelodysplastic Syndromes pathology, Neoplasm Proteins genetics, Neoplasms, Second Primary genetics, Neoplasms, Second Primary pathology, Proto-Oncogene Proteins genetics, Sex Distribution, Chromosomes, Human, X genetics, Isochromosomes, Leukemia, Myeloid genetics, Myelodysplastic Syndromes genetics
- Published
- 2019
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187. [A primitive plasma cell leukemia with immunoglobulin (Ig) E].
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Rachidi M, Lazarian G, Letestu R, Lusina D, Desbene C, Vidal V, Eclache V, Baran-Marszak F, Cymbalista F, and Fleury C
- Subjects
- Aged, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 complications, Humans, Leukemia, Plasma Cell immunology, Male, Prognosis, Immunoglobulin E blood, Leukemia, Plasma Cell blood, Leukemia, Plasma Cell diagnosis
- Abstract
We report here a case of primitive plasma cell leukemia with immunoglobulin (Ig) E. IgE myeloma is an exceptional variant of multiple myeloma, with a very poor prognosis. Its biological diagnosis requires specific analyzes in order to detect IgE gammopathy. Plasma cell leukemia (PCL) is also a very rare and very severe form of multiple myeloma. There are two variants: primitive PCL (pPCL) occurring de novo and secondary PCL (sPCL), evolution of a preexisting myeloma. Its diagnosis is essentially biological since it is defined by a blood plasmocytosis greater than 2 G/L or 20% of the leucocytes.
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- 2019
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188. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact.
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Baliakas P, Jeromin S, Iskas M, Puiggros A, Plevova K, Nguyen-Khac F, Davis Z, Rigolin GM, Visentin A, Xochelli A, Delgado J, Baran-Marszak F, Stalika E, Abrisqueta P, Durechova K, Papaioannou G, Eclache V, Dimou M, Iliakis T, Collado R, Doubek M, Calasanz MJ, Ruiz-Xiville N, Moreno C, Jarosova M, Leeksma AC, Panayiotidis P, Podgornik H, Cymbalista F, Anagnostopoulos A, Trentin L, Stavroyianni N, Davi F, Ghia P, Kater AP, Cuneo A, Pospisilova S, Espinet B, Athanasiadou A, Oscier D, Haferlach C, and Stamatopoulos K
- Subjects
- Aged, Female, Follow-Up Studies, Humans, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Male, Middle Aged, Prognosis, Retrospective Studies, Somatic Hypermutation, Immunoglobulin genetics, Survival Rate, Tumor Suppressor Protein p53 genetics, Biomarkers, Tumor genetics, Chromosome Aberrations, Cytogenetics methods, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Mutation
- Abstract
Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with ≥5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcomes, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and/or TP53 mutations [ TP53 abs]), and the expression of somatically hypermutated (M-CLL) or unmutated immunoglobulin heavy variable genes. Thus, they contrasted with CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53 abs. At the other end of the spectrum, patients with CK and +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53 abs, and immunoglobulin heavy variable gene somatic hypermutation status, we propose a novel hierarchical model in which patients with high-CK exhibit the worst prognosis, whereas those with mutated CLL lacking CK or TP53 abs, as well as CK with +12,+19, show the longest overall survival. Thus, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with ≥5 chromosomal aberrations emerges as prognostically adverse, independent of other biomarkers. Prospective clinical validation is warranted before ultimately incorporating high-CK in risk stratification of CLL., (© 2019 by The American Society of Hematology.)
- Published
- 2019
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189. Genetic analysis of therapy-related myeloid neoplasms occurring after intensive treatment for acute promyelocytic leukemia.
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Renneville A, Attias P, Thomas X, Bally C, Hayette S, Farhat H, Eclache V, Marceau-Renaut A, Cassinat B, Feuillard J, Terré C, Delabesse E, Park S, Lejeune J, Chevret S, Adès L, Preudhomme C, and Fenaux P
- Subjects
- Adult, Alleles, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Genetic Testing, Humans, Leukemia, Promyelocytic, Acute therapy, Middle Aged, Mutation, Radiotherapy methods, Antineoplastic Combined Chemotherapy Protocols adverse effects, Genetic Variation, Leukemia, Promyelocytic, Acute complications, Leukemia, Promyelocytic, Acute genetics, Neoplasms, Second Primary diagnosis, Neoplasms, Second Primary etiology, Radiotherapy adverse effects
- Published
- 2018
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- View/download PDF
190. "Double-hit" chronic lymphocytic leukemia: An aggressive subgroup with 17p deletion and 8q24 gain.
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Chapiro E, Lesty C, Gabillaud C, Durot E, Bouzy S, Armand M, Le Garff-Tavernier M, Bougacha N, Struski S, Bidet A, Laharanne E, Barin C, Veronese L, Prié N, Eclache V, Gaillard B, Michaux L, Lefebvre C, Gaillard JB, Terré C, Penther D, Bastard C, Nadal N, Fert-Ferrer S, Auger N, Godon C, Sutton L, Tournilhac O, Susin SA, and Nguyen-Khac F
- Subjects
- Abnormal Karyotype, Adult, Aged, Aged, 80 and over, Disease-Free Survival, Female, Genes, p53, Humans, In Situ Hybridization, Fluorescence, Kaplan-Meier Estimate, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Male, Middle Aged, Neoplasm Invasiveness genetics, Prognosis, Retrospective Studies, Chromosome Deletion, Chromosomes, Human, Pair 17 ultrastructure, Chromosomes, Human, Pair 8 ultrastructure, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Translocation, Genetic, Trisomy
- Abstract
Chronic lymphocytic leukemia (CLL) with 17p deletion (17p-) is associated with a lack of response to standard treatment and thus the worst possible clinical outcome. Various chromosomal abnormalities (including unbalanced translocations, deletions, ring chromosomes and isochromosomes) result in the loss of 17p and one copy of the TP53 gene. The objective of the present study was to determine whether the type of chromosomal abnormality leading to 17p- and the additional aberrations influenced the prognosis in a series of 195 patients with 17p-CLL. Loss of 17p resulted primarily from an unbalanced translocation (70%) with several chromosome partners (the most frequent being chromosome 18q), followed by deletion 17p (23%), monosomy 17 (8%), isochromosome 17q [i(17q)] (5%) and a ring chromosome 17 (2%). In a univariate analysis, monosomy 17, a highly complex karyotype (≥5 abnormalities), and 8q24 gain were associated with poor treatment-free survival, and i(17q) (P = .04), unbalanced translocations (P = .03) and 8q24 gain (P = .001) were significantly associated with poor overall survival. In a multivariate analysis, 8q24 gain remained a significant predictor of poor overall survival. We conclude that 17p deletion and 8q24 gain have a synergistic impact on outcome, and so patients with this "double-hit" CLL have a particularly poor prognosis. Systematic, targeting screening for 8q24 gain should therefore be considered in cases of 17p- CLL., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2018
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191. Old DAT and new data: positive direct antiglobulin test identifies a subgroup with poor outcome among chronic lymphocytic leukemia stage A patients.
- Author
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Quinquenel A, Al Nawakil C, Baran-Marszak F, Eclache V, Letestu R, Khalloufi M, Boubaya M, Le Roy C, Varin-Blank N, Delmer A, Levy V, and Ajchenbaum-Cymbalista F
- Subjects
- Adult, Aged, Aged, 80 and over, Anemia, Hemolytic, Autoimmune etiology, Anemia, Hemolytic, Autoimmune immunology, Anemia, Hemolytic, Autoimmune mortality, Cohort Studies, Complement C3d analysis, Data Interpretation, Statistical, Disease Progression, Disease-Free Survival, Female, Follow-Up Studies, Humans, Immunoglobulin G blood, Kaplan-Meier Estimate, Leukemia, Lymphocytic, Chronic, B-Cell complications, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Middle Aged, Predictive Value of Tests, Prognosis, Anemia, Hemolytic, Autoimmune diagnosis, Coombs Test, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis
- Abstract
Only a minority of chronic lymphocytic leukemia (CLL) patients harboring a positive direct antiglobulin test (DAT) will develop autoimmune hemolytic anemia (AIHA). In a single institution cohort of 378 CLL patients, 56 patients (14.8%) had at least one positive DAT during the course of the disease, either at diagnosis or later. We found no relationship between the time of the first positive DAT and overall survival (OS). However, patients with a positive DAT who did not develop AIHA had the same adverse outcome as patients who developed AIHA. Of the patients who were in Binet stage A at diagnosis, those with a positive DAT had a significantly shorter OS, regardless of their IGHV mutational status, however, there was a strong association with VH1-69. By multivariate analysis, a positive DAT was found to be an independent adverse prognostic factor for OS. Thus, DAT represents a strong adverse prognostic factor and its determination should be repeated during follow-up., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2015
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192. 14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV genes in chronic lymphocytic leukemia and small lymphocytic lymphoma.
- Author
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Cosson A, Chapiro E, Belhouachi N, Cung HA, Keren B, Damm F, Algrin C, Lefebvre C, Fert-Ferrer S, Luquet I, Gachard N, Mugneret F, Terre C, Collonge-Rame MA, Michaux L, Rafdord-Weiss I, Talmant P, Veronese L, Nadal N, Struski S, Barin C, Helias C, Lafage M, Lippert E, Auger N, Eclache V, Roos-Weil D, Leblond V, Settegrana C, Maloum K, Davi F, Merle-Beral H, Lesty C, and Nguyen-Khac F
- Subjects
- Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 12 genetics, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Male, Middle Aged, Mutation, Chromosomes, Human, Pair 14 genetics, Immunoglobulin Heavy Chains genetics, Immunoglobulin Variable Region genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Receptor, Notch1 genetics, Trisomy genetics
- Abstract
Deletions of the long arm of chromosome 14 [del(14q)] are rare but recurrently observed in mature B-cell neoplasms, particularly in chronic lymphocytic leukemia (CLL). To further characterize this aberration, we studied 81 cases with del(14q): 54 of CLL and 27 of small lymphocytic lymphoma (SLL), the largest reported series to date. Using karyotype and fluorescence in situ hybridization (FISH), the most frequent additional abnormality was trisomy 12 (tri12), observed in 28/79 (35%) cases, followed by del13q14 (12/79, 15%), delTP53 (11/80, 14%) delATM (5/79, 6%), and del6q21 (3/76, 4%). IGHV genes were unmutated in 41/53 (77%) patients, with a high frequency of IGHV1-69 (21/52, 40%). NOTCH1 gene was mutated in 14/45 (31%) patients. There was no significant difference in cytogenetic and molecular abnormalities between CLL and SLL. Investigations using FISH and SNP-array demonstrated the heterogeneous size of the 14q deletions. However, a group with the same del(14)(q24.1q32.33) was identified in 48% of cases. In this group, tri12 (P = 0.004) and NOTCH1 mutations (P = 0.02) were significantly more frequent than in the other patients. In CLL patients with del(14q), median treatment-free survival (TFS) was 27 months. In conclusion, del(14q) is associated with tri12 and with pejorative prognostic factors: unmutated IGHV genes (with over-representation of the IGHV1-69 repertoire), NOTCH1 mutations, and a short TFS., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2014
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193. Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström's macroglobulinemia.
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Nguyen-Khac F, Lambert J, Chapiro E, Grelier A, Mould S, Barin C, Daudignon A, Gachard N, Struski S, Henry C, Penther D, Mossafa H, Andrieux J, Eclache V, Bilhou-Nabera C, Luquet I, Terre C, Baranger L, Mugneret F, Chiesa J, Mozziconacci MJ, Callet-Bauchu E, Veronese L, Blons H, Owen R, Lejeune J, Chevret S, Merle-Beral H, and Leblondon V
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents therapeutic use, Chlorambucil therapeutic use, Chromosome Deletion, Chromosomes, Human, Pair 11 genetics, Chromosomes, Human, Pair 13 genetics, Chromosomes, Human, Pair 17 genetics, Chromosomes, Human, Pair 18 genetics, Chromosomes, Human, Pair 4 genetics, Chromosomes, Human, Pair 6 genetics, Female, Humans, In Situ Hybridization, Fluorescence, Kaplan-Meier Estimate, Karyotype, Male, Middle Aged, Prognosis, Prospective Studies, Trisomy, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Waldenstrom Macroglobulinemia drug therapy, Waldenstrom Macroglobulinemia pathology, Chromosome Aberrations, Waldenstrom Macroglobulinemia genetics
- Abstract
Waldenström's macroglobulinemia is a disease of mature B cells, the genetic basis of which is poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. We conducted a prospective cytogenetic study of Waldenström's macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomized trial. The main aberrations were 6q deletions (30%), trisomy 18 (15%), 13q deletions (13%), 17p (TP53) deletions (8%), trisomy 4 (8%), and 11q (ATM) deletions (7%). There was a significant association between trisomy of chromosome 4 and trisomy of chromosome 18. Translocations involving the IGH genes were rare (<5%). Deletion of 6q and 11q, and trisomy 4, were significantly associated with adverse clinical and biological parameters. Patients with TP53 deletion had short progression-free survival and short disease-free survival. Although rare (<5%), trisomy 12 was associated with short progression-free survival. In conclusion, the cytogenetic profile of Waldenström's macroglobulinemia appears to differ from that of other B-cell lymphomas. Chromosomal abnormalities may help with diagnosis and prognostication, in conjunction with other clinical and biological characteristics.
- Published
- 2013
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194. Neurofibromatosis-1 gene deletions and mutations in de novo adult acute myeloid leukemia.
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Boudry-Labis E, Roche-Lestienne C, Nibourel O, Boissel N, Terre C, Perot C, Eclache V, Gachard N, Tigaud I, Plessis G, Cuccuini W, Geffroy S, Villenet C, Figeac M, Leprêtre F, Renneville A, Cheok M, Soulier J, Dombret H, and Preudhomme C
- Subjects
- Adolescent, Adult, Aged, Alleles, Comparative Genomic Hybridization, Female, Gene Frequency, High-Throughput Nucleotide Sequencing, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Male, Middle Aged, Mutation Rate, Neurofibromin 1 deficiency, Real-Time Polymerase Chain Reaction, Gene Deletion, Leukemia, Myeloid, Acute genetics, Neurofibromatosis 1 genetics, Neurofibromin 1 genetics
- Abstract
Germline heterozygous alterations of the tumor-suppressor gene neurofibromatosis-1 (NF1) lead to neurofibromatosis type 1, a genetic disorder characterized by a higher risk to develop juvenile myelomonocytic leukemia and/or acute myeloid leukemia (AML). More recently, somatic 17q11 deletions encompassing NF1 have been described in many adult myeloid malignancies. In this context, we aimed to define NF1 involvement in AML. We screened a total of 488 previously untreated de novo AML patients for the NF1 deletion using either array comparative genomic hybridization (aCGH) or real-time quantitative PCR/fluorescence in situ hybridization approaches. We also applied massively parallel sequencing for in depth mutation analysis of NF1 in 20 patients including five NF1-deleted patients. We defined a small ∼0.3 Mb minimal deleted region involving NF1 by aCGH and an overall frequency of NF1 deletion of 3.5% (17/485). NF1 deletion is significantly associated with unfavorable cytogenetics and with monosomal karyotype notably. We discovered six NF1 variants of unknown significance in 7/20 patients of which only one out of four disappeared in corresponding complete remission sample. In addition, only one out of five NF1-deleted patients has an acquired coding mutation in the remaining allele. In conclusion, direct NF1 inactivation is infrequent in de novo AML and may be a secondary event probably involved in leukemic progression., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2013
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195. Treatment with lenalidomide does not appear to increase the risk of progression in lower risk myelodysplastic syndromes with 5q deletion. A comparative analysis by the Groupe Francophone des Myelodysplasies.
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Adès L, Le Bras F, Sebert M, Kelaidi C, Lamy T, Dreyfus F, Eclache V, Delaunay J, Bouscary D, Visanica S, Turlure P, Bresler AG, Cabrol MP, Banos A, Blanc M, Vey N, Delmer A, Wattel E, Chevret S, and Fenaux P
- Subjects
- Adult, Aged, Aged, 80 and over, Cohort Studies, Female, France epidemiology, Humans, Lenalidomide, Male, Middle Aged, Myelodysplastic Syndromes chemically induced, Survival Rate, Thalidomide adverse effects, Thalidomide therapeutic use, Treatment Outcome, Chromosome Deletion, Chromosomes, Human, Pair 5 genetics, Disease Progression, Myelodysplastic Syndromes epidemiology, Myelodysplastic Syndromes genetics, Thalidomide analogs & derivatives
- Abstract
Background: Although lenalidomide is very effective in the treatment of anemia of lower risk myelodysplastic syndromes with 5q deletion (del 5q), concerns have been raised over the fact that this drug could trigger progression to acute myeloid leukemia in some patients., Design and Methods: Ninety-five transfusion-dependent patients with lower risk myelodysplastic syndromes with del 5q were treated with lenalidomide (10 mg/day, for 3 weeks every 4 weeks); six (6.3%) of the patients progressed to acute myeloid leukemia. This cohort of 95 lenalidomide-treated patients was compared to a historical control cohort of 99 patients with lower risk myelodysplastic syndromes with del 5q who never received lenalidomide, using a propensity score approach that can control for potential confounders in non-randomized comparisons., Results: The 4-year estimated cumulative incidence of leukemia was 9% in patients treated with lenalidomide and 15.8% in controls who did not receive lenalidomide (P=0.16)., Conclusions: Using a propensity score approach, we found no significant difference in acute myeloid leukemia progression and survival from diagnosis between the cohort treated with lenalidomide and the control cohort.
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- 2012
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196. Specific chromosomal IG translocations have different prognoses in chronic lymphocytic leukemia.
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Nguyen-Khac F, Chapiro E, Lesty C, Grelier A, Luquet I, Radford-Weiss I, Lefebvre C, Fert-Ferrer S, Callet-Bauchu E, Lippert E, Raggueneau V, Michaux L, Barin C, Collonge-Rame MA, Mugneret F, Eclache V, Taviaux S, Dastugue N, Richebourg S, Struski S, Talmant P, Baranger L, Gachard N, Gervais C, Quilichini B, Settegrana C, Maloum K, Davi F, and Merle-Béral H
- Abstract
Background: Chromosomal translocations are usually analyzed as a single entity, and are associated with a poor outcome in chronic lymphocytic leukemia. Translocations involving immunoglobulin genes are recurrent, but uncommon (<5%), and their individual prognosis is not clear. The two most frequent partners are BCL2 (18q21) and BCL3 (19q13)., Designs and Methods: Herein, 75 cases are reported of chronic lymphocytic leukemia and t(14;18) (BCL2-CLLs). Our series benefits from morphological, immunological and cytogenetical reviews. The IGHV status analyses were performed by referring laboratories. Comparison was made with our previously published series of chronic lymphocytic leukemia patients with t(14;19) (BCL3-CLLs, n=29)., Results: Compared with BCL3-CLLs, lymphocytosis was lower in BCL2-CLLs (p<0.008), and splenomegaly was less frequent (p<0.0001). There were more "typical" morphologies (p<0.005) and Matutes scores >4 (p<0.001) in the BCL2-CLLs group, and less CD38 expression (p<0.04). More variant BCL2-translocations were observed (t(18;22), n=11; 2t(2;18), n=2; p<0.02), and BCL2-translocation was frequently single (p<0.002). Complex karyotypes (p<0.02), trisomy 12 (p<0.03), 6q deletion (p<0.002) and TP53 deletion (p<0.02) were less frequent in BCL2-CLLs, whereas 13q deletion was more frequent (p<0.005). The IGHV gene was frequently mutated in BCL2-CLLs (p<0.0001). Treatment-free survival was longer in BCL2-CLLs (p<0.0001)., Conclusions: BCL2-CLL.S express CD5 and lack expression of CD38, and have a Matutes score ≥4, frequent trisomy 12, no ATM and 6q deletions, and a mutated IGHV status. Compared to BCL3-CLLs, BCL2-CLLs are much less aggressive; indicating that identifying individual translocations and cytogenetic partners would allow improved patient stratification.
- Published
- 2011
197. Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia.
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Preudhomme C, Guilhot J, Nicolini FE, Guerci-Bresler A, Rigal-Huguet F, Maloisel F, Coiteux V, Gardembas M, Berthou C, Vekhoff A, Rea D, Jourdan E, Allard C, Delmer A, Rousselot P, Legros L, Berger M, Corm S, Etienne G, Roche-Lestienne C, Eclache V, Mahon FX, and Guilhot F
- Subjects
- Adult, Anemia chemically induced, Antineoplastic Combined Chemotherapy Protocols adverse effects, Benzamides, Cytarabine administration & dosage, Cytarabine adverse effects, Female, Fusion Proteins, bcr-abl analysis, Fusion Proteins, bcr-abl genetics, Humans, Imatinib Mesylate, Interferon alpha-2, Interferon-alpha adverse effects, Leukemia, Myeloid, Chronic-Phase mortality, Leukemia, Myeloid, Chronic-Phase pathology, Male, Middle Aged, Neutropenia chemically induced, Piperazines adverse effects, Polyethylene Glycols adverse effects, Proto-Oncogene Proteins c-abl analysis, Proto-Oncogene Proteins c-abl genetics, Pyrimidines adverse effects, RNA, Neoplasm analysis, Recombinant Proteins, Remission Induction, Stem Cells drug effects, Survival Analysis, Thrombocytopenia chemically induced, Transcription, Genetic, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Interferon-alpha administration & dosage, Leukemia, Myeloid, Chronic-Phase drug therapy, Piperazines administration & dosage, Polyethylene Glycols administration & dosage, Pyrimidines administration & dosage
- Abstract
Background: Imatinib (400 mg daily) is considered the best initial therapy for patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase. However, only a minority of patients treated with imatinib have a complete molecular remission., Methods: We randomly assigned 636 patients with untreated chronic-phase CML to receive imatinib alone at a dose of 400 mg daily, imatinib (400 mg daily) plus cytarabine (20 mg per square meter of body-surface area per day on days 15 through 28 of each 28-day cycle) or pegylated interferon (peginterferon) alfa-2a (90 μg weekly), or imatinib alone at a dose of 600 mg daily. Molecular and cytogenetic responses, time to treatment failure, overall and event-free survival, and adverse events were assessed. An analysis of molecular response at 12 months was planned. A superior molecular response was defined as a decrease in the ratio of transcripts of the tyrosine kinase gene BCR-ABL to transcripts of ABL of 0.01% or less, corresponding to a reduction of 4 log(10) units or more from the baseline level, as assessed by means of a real-time quantitative polymerase-chain-reaction assay., Results: At 12 months, the rates of cytogenetic response were similar among the four groups. The rate of a superior molecular response was significantly higher among patients receiving imatinib and peginterferon alfa-2a (30%) than among patients receiving 400 mg of imatinib alone (14%) (P=0.001). The rate was significantly higher among patients treated for more than 12 months than among those treated for 12 months or less. Gastrointestinal events were more frequent among patients receiving cytarabine, whereas rash and depression were more frequent among patients receiving peginterferon alfa-2a., Conclusions: As compared with other treatments, the addition of peginterferon alfa-2a to imatinib therapy resulted in significantly higher rates of molecular response in patients with chronic-phase CML. (Funded by the French Ministry of Health and others; ClinicalTrials.gov number, NCT00219739.).
- Published
- 2010
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198. Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM).
- Author
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Thepot S, Itzykson R, Seegers V, Raffoux E, Quesnel B, Chait Y, Sorin L, Dreyfus F, Cluzeau T, Delaunay J, Sanhes L, Eclache V, Dartigeas C, Turlure P, Harel S, Salanoubat C, Kiladjian JJ, Fenaux P, and Adès L
- Subjects
- Adult, Aged, Aged, 80 and over, Disease Progression, Female, France epidemiology, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Myelodysplastic Syndromes mortality, Myeloproliferative Disorders genetics, Philadelphia Chromosome, Prognosis, Treatment Outcome, Antimetabolites, Antineoplastic therapeutic use, Azacitidine therapeutic use, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute etiology, Myelodysplastic Syndromes drug therapy, Myelodysplastic Syndromes etiology, Myeloproliferative Disorders complications, Myeloproliferative Disorders drug therapy
- Abstract
Transformation of Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs) to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) is associated with poor response to chemotherapy and short survival. Fifty-four patients with Ph-negative MPN (including 21 essential thrombocythemia [ET], 21 polycythemia vera [PV], 7 primary myelofibrosis, and 5 unclassified MPN) who had progressed to AML (n = 26) or MDS (n = 28) were treated with azacitidine in a patient-named program. Overall response rate was 52% (24% complete response [CR], 11% partial response [PR], 8% marrow CR or CR with incomplete recovery of cytopenias, 9% hematologic improvement) and median response duration was 9 months. Prognostic factors were for overall response the underlying MPN (71% vs 33% responses in ET and PV, respectively; P = .016); prognostic factors for CR achievement were the underlying MPN (14% CR for PV vs 43% for ET; P = .040) and World Health Organization classification at transformation (36% vs 12% CR in MDS and AML, respectively, P = .038). Recurrence of chronic phase features of the initial MPN was observed in 39% of the responders. Median overall survival was 11 months. Azacitidine gives encouraging results in Ph-negative MPN having progressed to AML or MDS, but response duration is short, and consolidation treatments have to be evaluated.
- Published
- 2010
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199. Loss of the Y chromosome in Philadelphia-positive cells predicts a poor response of chronic myeloid leukemia patients to imatinib mesylate therapy.
- Author
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Lippert E, Etienne G, Mozziconacci MJ, Laibe S, Gervais C, Girault S, Gachard N, Tigaud I, Dastugue N, Huguet F, Fort MP, Legros L, Eclache V, and Mahon FX
- Subjects
- Benzamides, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Male, Prognosis, Retrospective Studies, Survival Analysis, Chromosome Aberrations, Chromosomes, Human, Y, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Piperazines therapeutic use, Pyrimidines therapeutic use
- Abstract
In chronic myeloid leukemia (CML), cytogenetic abnormalities found in addition to the t(9;22) translocation may impact the response to therapy. Loss of the Y chromosome is generally overlooked in this context, owing to its relatively frequent occurrence in healthy elderly patients. In this multicenter retrospective study, the outcome after imatinib treatment of 30 CML patients with karyotype showing Y chromosome loss (Y-) was compared to 30 Y+ control males diagnosed and treated at the same time in the same institutions. Y- patients had significantly delayed cytogenetic and molecular responses, lower event-free survival and shorter overall survival than Y+ patients. The negative impact of this abnormality was particularly marked when it occurred in a sub-clone (clonal evolution) rather than in all mitoses. These data indicate that loss of the Y chromosome should be taken into account in the prognostic evaluation of chronic myelogenous leukemia patients.
- Published
- 2010
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200. Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study.
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Coyaud E, Struski S, Prade N, Familiades J, Eichner R, Quelen C, Bousquet M, Mugneret F, Talmant P, Pages MP, Lefebvre C, Penther D, Lippert E, Nadal N, Taviaux S, Poppe B, Luquet I, Baranger L, Eclache V, Radford I, Barin C, Mozziconacci MJ, Lafage-Pochitaloff M, Antoine-Poirel H, Charrin C, Perot C, Terre C, Brousset P, Dastugue N, and Broccardo C
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Chromosome Breakpoints, Chromosomes, Human, Pair 9 genetics, Cloning, Molecular, Cohort Studies, Female, France, Gene Expression Regulation, Leukemic, Humans, Karyotyping, Male, Middle Aged, Oncogene Proteins, Fusion genetics, Oncogene Proteins, Fusion metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, Young Adult, Cytogenetic Analysis, Mutation genetics, PAX5 Transcription Factor genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
PAX5 is the main target of somatic mutations in acute B lymphoblastic leukemia (B-ALL). We analyzed 153 adult and child B-ALL harboring karyotypic abnormalities at chromosome 9p, to determine the frequency and the nature of PAX5 alterations. We found PAX5 internal rearrangements in 21% of the cases. To isolate fusion partners, we used classic and innovative techniques (rolling circle amplification-rapid amplification of cDNA ends) and single nucleotide polymorphism-comparative genomic hybridization arrays. Recurrent and novel fusion partners were identified, including NCoR1, DACH2, GOLGA6, and TAOK1 genes showing the high variability of the partners. We noted that half the fusion genes can give rise to truncated PAX5 proteins. Furthermore, malignant cells carrying PAX5 fusion genes displayed a simple karyotype. These data strongly suggest that PAX5 fusion genes are early players in leukemogenesis. In addition, PAX5 deletion was observed in 60% of B-ALL with 9p alterations. Contrary to cases with PAX5 fusions, deletions were associated with complex karyotypes and common recurrent translocations. This supports the hypothesis of the secondary nature of the deletion. Our data shed more light on the high variability of PAX5 alterations in B-ALL. Therefore, it is probable that gene fusions occur early, whereas deletions should be regarded as a late/secondary event.
- Published
- 2010
- Full Text
- View/download PDF
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