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10 results on '"Eclache, Virginie"'

1. The Broad Spectrum of TP53 Mutations in CLL : Evidence of Multiclonality and Novel Mutation Hotspots

Author

Lazarian, Gregory, Leroy, Bernard, Theves, Floriane, Hormi, Myriam, Letestu, Remi, Eclache, Virginie, Tueur, Giulia, Ameur, Adam, Bidet, Audrey, Cornillet-Lefebvre, Pascale, Davi, Frederic, Delabesse, Eric, Estienne, Marie-Helene, Etancelin, Pascaline, Kosmider, Olivier, Laibe, Sophy, Muller, Marc, Nadal, Nathalie, Naguib, Dina, Pastoret, Cedric, Poulain, Stephanie, Sujobert, Pierre, Veronese, Lauren, Imache, Samia, Lefebvre, Valerie, Cymbalista, Florence, Baran-Marszak, Fanny, Soussi, Thierry, Lazarian, Gregory, Leroy, Bernard, Theves, Floriane, Hormi, Myriam, Letestu, Remi, Eclache, Virginie, Tueur, Giulia, Ameur, Adam, Bidet, Audrey, Cornillet-Lefebvre, Pascale, Davi, Frederic, Delabesse, Eric, Estienne, Marie-Helene, Etancelin, Pascaline, Kosmider, Olivier, Laibe, Sophy, Muller, Marc, Nadal, Nathalie, Naguib, Dina, Pastoret, Cedric, Poulain, Stephanie, Sujobert, Pierre, Veronese, Lauren, Imache, Samia, Lefebvre, Valerie, Cymbalista, Florence, Baran-Marszak, Fanny, and Soussi, Thierry

Abstract

TP53 aberrations are a major predictive factor of resistance to chemoimmunotherapy in chronic lymphocytic leukemia (CLL), and an assessment of them before each line of treatment is required for theranostic stratification. Acquisition of subclonal TP53 abnormalities underlies the evolution of CLL. To better characterize the distribution, combination, and impact of TP53 variants in CLL, 1,056 TP53 variants collected from 683 patients included in a multicenter collaborative study in France were analyzed and compared to UMD_CLL, a dataset built from published articles collectively providing 5,173 TP53 variants detected in 3,808 patients. Our analysis confirmed the presence of several CLL-specific hotspot mutations, including a two-base pair deletion in codon 209 and a missense variant at codon 234, the latter being associated with alkylating treatment. Our analysis also identified a novel CLL-specific variant in the splice acceptor signal of intron 6 leading to the use of a cryptic splice site, similarly utilized by TP53 to generate p53psi, a naturally truncated p53 isoform localized in the mitochondria. Examination of both UMD_CLL and several recently released large-scale genomic analyses of CLL patients confirmed that this splice variant is highly enriched in this disease when compared to other cancer types. Using a TP53-specific single-nucleotide polymorphism, we also confirmed that copy-neutral loss of heterozygosity is frequent in CLL. This event can lead to misinterpretation of TP53 status. Unlike other cancers, CLL displayed a high proportion of patients harboring multiple TP53 variants. Using both in silico analysis and single molecule smart sequencing, we demonstrated the coexistence of distinct subclones harboring mutations on distinct alleles. In summary, our study provides a detailed TP53 mutational architecture in CLL and gives insights into how treatments may shape the genetic landscape of CLL patients.

Published
2023
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2. TP53 mutations at codon 234 are associated with chlorambucil treatment in chronic lymphocytic leukemia

Author

Lazarian, Gregory, Theves, Floriane, Hormi, Myriam, Letestu, Remi, Eclache, Virginie, Bidet, Audrey, Cornillet-Lefebvre, Pascale, Davi, Frederic, Delabesse, Eric, Estienne, Marie-Helene, Etancelin, Pascaline, Kosmider, Olivier, Laibe, Sophy, Lode, Laurence, Muller, Marc, Nadal, Nathalie, Naguib, Dina, Pastoret, Cedric, Poulain, Stephanie, Sujobert, Pierre, Veronese, Lauren, Imache, Samia, Lefebvre, Valerie, Cymbalista, Florence, Baran-Marszak, Fanny, Soussi, Thierry, Lazarian, Gregory, Theves, Floriane, Hormi, Myriam, Letestu, Remi, Eclache, Virginie, Bidet, Audrey, Cornillet-Lefebvre, Pascale, Davi, Frederic, Delabesse, Eric, Estienne, Marie-Helene, Etancelin, Pascaline, Kosmider, Olivier, Laibe, Sophy, Lode, Laurence, Muller, Marc, Nadal, Nathalie, Naguib, Dina, Pastoret, Cedric, Poulain, Stephanie, Sujobert, Pierre, Veronese, Lauren, Imache, Samia, Lefebvre, Valerie, Cymbalista, Florence, Baran-Marszak, Fanny, and Soussi, Thierry

Published
2022
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3. Clinical and biological characteristics of leukemia cutis in chronic lymphocytic leukemia: A study of the French innovative leukemia organization (FILO).

Author

UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre du cancer, Lazarian, Grégory, Munger, Michaël, Quinquenel, Anne, Dilhuydy, Marie-Sarah, Veronese, Lauren, Luque Paz, Damien, Guièze, Romain, Ledoux-Pilon, Albane, Paillassa, Jérôme, Merabet, Fatiha, Vial, Jean-Philippe, Bidet, Audrey, Waultier Rascalou, Agathe, Broseus, Julien, Roos-Weil, Damien, Lavaud, Anne, Molina, Lysiane, Laribi, Kamel, Hivert, Bénédicte, Friedrich, Chloé, Carpentier, Benjamin, Ysebaert, Loïc, Van Den Neste, Eric, Willems, Lise, Corby, Anne, Poulain, Stéphanie, Eclache, Virginie, Maubec, Eve, Martin, Antoine, Feugier, Pierre, Delmer, Alain, Baran-Marszak, Fanny, Leprêtre, Stéphane, Cymbalista, Florence, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre du cancer, Lazarian, Grégory, Munger, Michaël, Quinquenel, Anne, Dilhuydy, Marie-Sarah, Veronese, Lauren, Luque Paz, Damien, Guièze, Romain, Ledoux-Pilon, Albane, Paillassa, Jérôme, Merabet, Fatiha, Vial, Jean-Philippe, Bidet, Audrey, Waultier Rascalou, Agathe, Broseus, Julien, Roos-Weil, Damien, Lavaud, Anne, Molina, Lysiane, Laribi, Kamel, Hivert, Bénédicte, Friedrich, Chloé, Carpentier, Benjamin, Ysebaert, Loïc, Van Den Neste, Eric, Willems, Lise, Corby, Anne, Poulain, Stéphanie, Eclache, Virginie, Maubec, Eve, Martin, Antoine, Feugier, Pierre, Delmer, Alain, Baran-Marszak, Fanny, Leprêtre, Stéphane, and Cymbalista, Florence

Abstract

TO THE EDITOR : Patients with chronic lymphocytic leukemia (CLL) exhibit a variety of skin lesions including mostly non-specific cutaneous manifestations (such as cutaneous infections or exaggerated reactions to insect bite) and secondary cutaneous malignancies, as patients are at high risk of developing basal cell carcinoma, squamous cell carcinoma, melanoma, and Merkel cell carcinoma. Specific cutaneous infiltration by neoplastic B lymphocytes with clinically identifiable skin lesions, also called leukemia cutis (LC), is more uncommon and has seldom been reported in chronic lymphocytic leukemia. [...]

Published
2021

4. Prevalence, distribution and predictive value of XPO1 mutation in a real-life chronic lymphocytic leukaemia cohort.

Author

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, Baran-Marszak, Fanny, 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

Published
2020
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5. Cytogenetic complexity in chronic lymphocytic leukemia : definitions, associations, and clinical impact

Author

Baliakas, Panagiotis, Jeromin, Sabine, Iskas, Michalis, Puiggros, Anna, Plevova, Karla, Nguyen-Khac, Florence, Davis, Zadie, Rigolin, Gian Matteo, Visentin, Andrea, Xochelli, Aliki, Delgado, Julio, Baran-Marszak, Fanny, Stalika, Evangelia, Abrisqueta, Pau, Durechova, Kristina, Papaioannou, George, Eclache, Virginie, Dimou, Maria, Iliakis, Theodoros, Collado, Rosa, Doubek, Michael, Jose Calasanz, M., Ruiz-Xiville, Neus, Moreno, Carolina, Jarosova, Marie, Leeksma, Alexander C., Panayiotidis, Panayiotis, Podgornik, Helena, Cymbalista, Florence, Anagnostopoulos, Achilles, Trentin, Livio, Stavroyianni, Niki, Davi, Fred, Ghia, Paolo, Kater, Arnon P., Cuneo, Antonio, Pospisilova, Sarka, Espinet, Blanca, Athanasiadou, Anastasia, Oscier, David, Haferlach, Claudia, Stamatopoulos, Kostas, Baliakas, Panagiotis, Jeromin, Sabine, Iskas, Michalis, Puiggros, Anna, Plevova, Karla, Nguyen-Khac, Florence, Davis, Zadie, Rigolin, Gian Matteo, Visentin, Andrea, Xochelli, Aliki, Delgado, Julio, Baran-Marszak, Fanny, Stalika, Evangelia, Abrisqueta, Pau, Durechova, Kristina, Papaioannou, George, Eclache, Virginie, Dimou, Maria, Iliakis, Theodoros, Collado, Rosa, Doubek, Michael, Jose Calasanz, M., Ruiz-Xiville, Neus, Moreno, Carolina, Jarosova, Marie, Leeksma, Alexander C., Panayiotidis, Panayiotis, Podgornik, Helena, Cymbalista, Florence, Anagnostopoulos, Achilles, Trentin, Livio, Stavroyianni, Niki, Davi, Fred, Ghia, Paolo, Kater, Arnon P., Cuneo, Antonio, Pospisilova, Sarka, Espinet, Blanca, Athanasiadou, Anastasia, Oscier, David, Haferlach, Claudia, and Stamatopoulos, Kostas

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 [TP53abs]), 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 TP53abs. At the other end of the spectrum, patients with CK and 112,119 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hyper-mutation 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 TP53abs, as well as CK with 112,119, 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.

Published
2019
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6. Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving and MYC and TP53

Author

Chapiro, Elise; https://orcid.org/0000-0003-3427-7596, Pramil, Elodie, Diop, M'boyba, Roos-Weil, Damien; https://orcid.org/0000-0002-7767-755X, Dillard, Clémentine, Gabillaud, Clémentine, Maloum, Karim; https://orcid.org/0000-0001-8864-4801, Settegrana, Catherine, Baseggio, Lucile; https://orcid.org/0000-0001-7543-6480, Lesesve, Jean-François, Yon, Mélanie, Jondreville, Ludovic, Lesty, Claude, Davi, Frederic; https://orcid.org/0000-0002-3764-063X, Le Garff-Tavernier, Magali; https://orcid.org/0000-0002-3131-3240, Droin, Nathalie, Dessen, Philippe, Algrin, Caroline, Leblond, Veronique, Gabarre, Jean, Bouzy, Simon, Eclache, Virginie, Gaillard, Baptiste, Callet-Bauchu, Evelyne, Muller, Marc, Lefebvre, Christine, Nadal, Nathalie, Ittel, Antoine, Struski, Stephanie, Collonge-Rame, Marie-Agnès, et al, Chapiro, Elise; https://orcid.org/0000-0003-3427-7596, Pramil, Elodie, Diop, M'boyba, Roos-Weil, Damien; https://orcid.org/0000-0002-7767-755X, Dillard, Clémentine, Gabillaud, Clémentine, Maloum, Karim; https://orcid.org/0000-0001-8864-4801, Settegrana, Catherine, Baseggio, Lucile; https://orcid.org/0000-0001-7543-6480, Lesesve, Jean-François, Yon, Mélanie, Jondreville, Ludovic, Lesty, Claude, Davi, Frederic; https://orcid.org/0000-0002-3764-063X, Le Garff-Tavernier, Magali; https://orcid.org/0000-0002-3131-3240, Droin, Nathalie, Dessen, Philippe, Algrin, Caroline, Leblond, Veronique, Gabarre, Jean, Bouzy, Simon, Eclache, Virginie, Gaillard, Baptiste, Callet-Bauchu, Evelyne, Muller, Marc, Lefebvre, Christine, Nadal, Nathalie, Ittel, Antoine, Struski, Stephanie, Collonge-Rame, Marie-Agnès, and et al

Abstract

B-cell prolymphocytic leukemia (B-PLL) is a rare hematological disorder whose underlying oncogenic mechanisms are poorly understood. Our cytogenetic and molecular assessment of 34 patients with B-PLL revealed several disease-specific features and potential therapeutic targets. The karyotype was complex ({greater than or equal to}3 abnormalities) in 73% of the patients and highly complex (5 abnormalities) in 45%. The most frequent chromosomal aberrations were translocations involving [t()] (62%), deletion (del)17p (38%), trisomy (tri)18 (30%), del13q (29%), tri3 (24%), tri12 (24%), and del8p (23%). Twenty-six of the 34 patients (76%) exhibit aberration, resulting from mutually exclusive translocations or gains. Whole-exome sequencing revealed frequent mutations in , , , , , , , , and The majority of B-PLL used the or subgroups (89%), and displayed significantly mutated genes (79%). We identified three distinct cytogenetic risk groups: low-risk (no aberration), intermediate-risk ( aberration but no del17p), and high-risk ( aberration and del17p) (p=.0006). drug response profiling revealed that the combination of a B-cell receptor or BCL2 inhibitor with OTX015 (a bromodomain and extra-terminal motif (BET) inhibitor targeting ) was associated with significantly lower viability of B-PLL cells harboring a t(). We conclude that cytogenetic analysis is a useful diagnostic and prognostic tool in B-PLL. Targeting may be a useful treatment option in this disease.

Published
2019

7. Value of cytogenetic abnormalities in adults with Ph-negative B-cell precursor acute lymphoblastic leukemia.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Centre de génétique médicale UCL, 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, Graux, Carlos, Huguet, Françoise, Lhéritier, Véronique, Ifrah, Norbert, Dombret, Hervé, Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)., UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Centre de génétique médicale UCL, 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, Graux, Carlos, Huguet, Françoise, Lhéritier, Véronique, Ifrah, Norbert, Dombret, Hervé, and Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL).

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 GRAALL-2003/2005 trials. Combined data from karyotype, DNA index, FISH and/or PCR screening for relevant abnormalities were centrally reviewed and were informative in 542 cases (88%), allowing classification in ten exclusive primary cytogenetic subgroups and in secondary subgroups including complex and monosomal karyotypes. Prognostic analyses focused on cumulative incidence of failure (including primary refractoriness and relapse), event-free survival and overall survival. Only two subgroups, namely t(4;11)/KMT2A-AFF1 and 14q32/IGH translocations, displayed a significant 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 SCT time. A worse 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 and monosomal karyotypes, had no prognostic value in these intensive protocols designed for adult patients up to the age of 60 years.

Published
2017

8. 14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV genes in chronic lymphocytic leukemia and small lymphocytic lymphoma

Author

UCL - (SLuc) Service d'hématologie, Cosson, Adrien, Chapiro, Elise, Belhouachi, Nabila, Cung, Hong-Anh, Keren, Boris, Damm, Frederik, Algrin, Caroline, Lefebvre, Christine, Fert-Ferrer, Sandra, Luquet, Isabelle, Gachard, Nathalie, Mugneret, Francine, Terre, Christine, Collonge-Rame, Marie-Agnes, Michaux, Lucienne, Rafdord-Weiss, Isabelle, Talmant, Pascaline, Veronese, Lauren, Nadal, Nathalie, Struski, Stephanie, Barin, Carole, Helias, Catherine, Lafage, Marina, Lippert, Eric, Auger, Nathalie, Eclache, Virginie, Roos-Weil, Damien, Leblond, Veronique, Settegrana, Catherine, Maloum, Karim, Davi, Frederic, Merle-Beral, Helene, Lesty, Claude, Nguyen-Khac, Florence, Groupe Francophone de Cytogénétique Hématologique, UCL - (SLuc) Service d'hématologie, Cosson, Adrien, Chapiro, Elise, Belhouachi, Nabila, Cung, Hong-Anh, Keren, Boris, Damm, Frederik, Algrin, Caroline, Lefebvre, Christine, Fert-Ferrer, Sandra, Luquet, Isabelle, Gachard, Nathalie, Mugneret, Francine, Terre, Christine, Collonge-Rame, Marie-Agnes, Michaux, Lucienne, Rafdord-Weiss, Isabelle, Talmant, Pascaline, Veronese, Lauren, Nadal, Nathalie, Struski, Stephanie, Barin, Carole, Helias, Catherine, Lafage, Marina, Lippert, Eric, Auger, Nathalie, Eclache, Virginie, Roos-Weil, Damien, Leblond, Veronique, Settegrana, Catherine, Maloum, Karim, Davi, Frederic, Merle-Beral, Helene, Lesty, Claude, Nguyen-Khac, Florence, and Groupe Francophone de Cytogénétique Hématologique

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.

Published
2014

9. Chronic lymphocytic leukemia and prolymphocytic leukemia with MYC translocations: a subgroup with an aggressive disease course

Author

UCL - SSS/DDUV - Institut de Duve, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre de génétique médicale UCL, Put, Natalie, Van 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, Quilichini, Benoît, Poirel, Hélène, Wlodarska, Iwona, Hagemeijer, Anne, Moreau, Yves, Vandenberghe, Peter, Michaux, Lucienne, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre de génétique médicale UCL, Put, Natalie, Van 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, Quilichini, Benoît, Poirel, Hélène, Wlodarska, Iwona, Hagemeijer, Anne, Moreau, Yves, Vandenberghe, Peter, and Michaux, Lucienne

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.

Published
2012

10. Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study

Author

UCL, Coyaud, Etienne, Struski, Stephanie, Prade, Nais, Familiades, Julien, Eichner, Ruth, Quelen, Cathy, Bousquet, Marina, Mugneret, Francine, Talmant, Pascaline, Pages, Marie-Pierre, Lefebvre, Christine, Penther, Dominique, Lippert, Eric, Nadal, Nathalie, Taviaux, Sylvie, Poppe, Bruce, Luquet, Isabelle, Baranger, Laurence, Eclache, Virginie, Radford, Isabelle, Barin, Carole, Mozziconacci, Marie-Joëlle, Lafage-Pochitaloff, Marina, Antoine-Poirel, Helene, Charrin, Christiane, Terre, Christine, Brousset, Pierre, Dastugue, Nicole, Broccardo, Cyril, UCL, Coyaud, Etienne, Struski, Stephanie, Prade, Nais, Familiades, Julien, Eichner, Ruth, Quelen, Cathy, Bousquet, Marina, Mugneret, Francine, Talmant, Pascaline, Pages, Marie-Pierre, Lefebvre, Christine, Penther, Dominique, Lippert, Eric, Nadal, Nathalie, Taviaux, Sylvie, Poppe, Bruce, Luquet, Isabelle, Baranger, Laurence, Eclache, Virginie, Radford, Isabelle, Barin, Carole, Mozziconacci, Marie-Joëlle, Lafage-Pochitaloff, Marina, Antoine-Poirel, Helene, Charrin, Christiane, Terre, Christine, Brousset, Pierre, Dastugue, Nicole, and Broccardo, Cyril

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. (Blood. 2010;115(15):3089-3097)

Published
2010

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