8 results on '"Eclache, Virginie"'
Search Results
2. 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
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- 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.)
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- 2019
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3. TP53 mutations are early events in chronic lymphocytic leukemia disease progression and precede evolution to complex karyotypes.
- Author
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Lazarian G, Tausch E, Eclache V, Sebaa A, Bianchi V, Letestu R, Collon JF, Lefebvre V, Gardano L, Varin-Blank N, Soussi T, Stilgenbauer S, Cymbalista F, and Baran-Marszak F
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- Disease Progression, Humans, In Situ Hybridization, Fluorescence, Karyotype, Leukemia, Lymphocytic, Chronic, B-Cell blood, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Longitudinal Studies, Retrospective Studies, Genes, p53, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Mutation, Tumor Suppressor Protein p53 genetics
- Abstract
TP53 abnormalities lead to resistance to purine analogues and are found in over 40% of patients with refractory chronic lymphocytic leukemia (CLL). At diagnosis, no more than 5% of patients carry the 17p deletion, most cases harbour mutations within the other TP53 allele. The incidence of a TP53 mutation as the only alteration is approximately 5%, but this depends on the sensitivity of the technique. Recently, having a complex karyotype has been considered a strong adverse prognostic factor. However, there are no longitudinal studies simultaneously examining the presence of the 17p deletion, TP53 mutations and karyotype abnormalities. We conducted a retrospective longitudinal study of 31 relapsed/refractory CLL patients. Two to six blood samples per patient were analyzed, with a median follow-up of 8 years. In this report, we assessed the sequence of events of TP53 clonal evolution and correlated the presence of TP53 abnormalities to genetic instability during progression and treatment. Next-generation sequencing allowed the early detection of TP53 mutated clones and was able to be performed on a routine basis, demonstrating an excellent correlation between the Illumina and Ion Torrent technologies. We concluded that TP53 mutations are early events and precede clonal evolution to complex karyotypes. We strongly recommend the early and iterated detection of TP53 mutations in progressive cases., (© 2016 UICC.)
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- 2016
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4. Prognostic value of TP53 gene mutations in myelodysplastic syndromes and acute myeloid leukemia treated with azacitidine.
- Author
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Bally C, Adès L, Renneville A, Sebert M, Eclache V, Preudhomme C, Mozziconacci MJ, de The H, Lehmann-Che J, and Fenaux P
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- Adult, Aged, Aged, 80 and over, Female, Humans, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Myelodysplastic Syndromes drug therapy, Myelodysplastic Syndromes mortality, Prognosis, Antimetabolites, Antineoplastic therapeutic use, Azacitidine therapeutic use, Genes, p53, Leukemia, Myeloid, Acute genetics, Mutation, Myelodysplastic Syndromes genetics
- 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 © 2014 Elsevier Ltd. All rights reserved.)
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- 2014
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5. Incidence of 17p deletions and TP53 mutation in myelodysplastic syndrome and acute myeloid leukemia with 5q deletion.
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Sebaa A, Ades L, Baran-Marzack F, Mozziconacci MJ, Penther D, Dobbelstein S, Stamatoullas A, Récher C, Prebet T, Moulessehoul S, Fenaux P, and Eclache V
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- Adult, Aged, Aged, 80 and over, Female, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Male, Middle Aged, Chromosome Deletion, Chromosomes, Human, Pair 5 genetics, Leukemia, Myeloid, Acute genetics, Mutation, Myelodysplastic Syndromes genetics, Tumor Suppressor Protein p53 genetics
- Abstract
TP53 mutations are frequent in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with complex karyotype that include del(5q) and are often associated with deletion of 17p. They have also recently been observed in MDS with isolated del(5q). We assessed the incidence of 17p deletion detected by fluorescence in situ hybridization (FISH) and of TP53 mutations detected by direct sequencing and their correlation and prognostic value in 26 MDS and 17 AML with del(5q). In the 20 cases with isolated del(5q) or one additional abnormality, no 17p deletion was found and 3 of the 18 cases analyzed (17%) had TP53 mutation. In the 23 patients with complex karyotype, 17p deletion was suspected by conventional cytogenetics in 15 cases and confirmed by FISH in 10 of them, while TP53 mutation was found in 8 of the 15 patients tested (53%), only five of whom had 17p deletion. In the whole patient series, TP53 mutations were associated with shorter survival (P = 0.07). We confirm the existence of TP53 mutations in 17% of MDS with isolated del(5q). In patients with del(5q) and complex karyotype, FISH and direct sequencing are complementary techniques to analyze TP53 abnormalities. Our findings also suggest that sequencing of the TP53 gene should be included in the study of patients with del(5q) as a single abnormality or in complex karyotype before lenalidomide treatment., (Copyright © 2012 Wiley Periodicals, Inc.)
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- 2012
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6. Chromosomal abnormalities in transformed Ph-negative myeloproliferative neoplasms are associated to the transformation subtype and independent of JAK2 and the TET2 mutations.
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Nguyen-Khac F, Lesty C, Eclache V, Couronné L, Kosmider O, Andrieux J, Collonge-Rame MA, Penther D, Lafage M, Bilhou-Nabera C, Chapiro E, Mozziconacci MJ, Mugneret F, Gachard N, Nadal N, Lippert E, Struski S, Dastugue N, Cabrol C, and Bernard OA
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- Adult, Aged, Aged, 80 and over, DNA Mutational Analysis, Dioxygenases, Female, Humans, Male, Middle Aged, Prognosis, Survival Rate, Young Adult, Cell Transformation, Neoplastic genetics, Chromosome Aberrations, DNA-Binding Proteins genetics, Janus Kinase 2 genetics, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative genetics, Mutation genetics, Proto-Oncogene Proteins genetics
- Abstract
Evolution to myelofibrosis (MF), acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) may occur over time in myeloproliferative neoplasms (MPN) patients most likely due to the acquisition of additional mutations. The Groupe Francophone de cytogenetique hematologique (GFCH) has collected and reviewed 82 patients with transformation of MPN (66 AML/MDS and 16 MF). JAK2V617F and TET2 mutations were searched for in 40 and 32 patients, respectively. Significantly more -7/del(7q) (P = 0.004) and -5/del(5q) (P = 0.03) were found in AML/MDS with a higher incidence of dup1q (P = 0.01) in MF. Some specific chromosomal abnormalities occurred together, for example -5/del(5q) and -17/del(17p) (P = 0.0007). In multivariate analysis, two factors were independently associated with an inferior overall survival (OS); AML/MDS transformation (P < 0.0001) and -5/del(5q) abnormality (P = 0.02). Although both giving rise to loss of 7q, der(1;7) differed from other 7q deletions in terms of distribution (lower frequency of AML/MDS, P = 0.02), association with chromosomal abnormalities (absence of -5/del(5q), P = 0.003; increased del(20q), P = 0.05), and longer OS (P = 0.0007). We detected 24/40 (60%) JAK2V617F and 8/25 (32%) TET2 mutations in samples following transformation, ranging from wild-type to mutated forms of both genes. The mutated and wild-type forms of the genes were not found to be associated with a specific chromosomal abnormality. There was no evidence that JAK2 or TET2 mutations were associated with the type of MPN transformation, whereas the type of cytogenetic abnormalities were strongly linked, perhaps indicating that they play a specific role in the transformation process.
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- 2010
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7. 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
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- 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.
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- 2010
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8. TP53 mutations at codon 234 are associated with chlorambucil treatment in chronic lymphocytic leukemia
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Lazarian, Grégory, Theves, Floriane, Hormi, Myriam, Letestu, Rémi, Eclache, Virginie, Bidet, Audrey, Cornillet-Lefebvre, Pascale, Davi, Frédéric, Delabesse, Eric, Estienne, Marie-Hélène, Etancelin, Pascaline, Kosmider, Olivier, Laibe, Sophy, Lode, Laurence, Muller, Marc, Nadal, Nathalie, Naguib, Dina, Pastoret, Cédric, Poulain, Stéphanie, Sujobert, Pierre, Veronese, Lauren, Imache, Samia, Lefebvre, Valérie, Cymbalista, Florence, Baran-Marszak, Fanny, Soussi, Thierry, Aurran, Thérese, Herbaux, Charles, Cartron, Guillaume, Dartigeas, Caroline, Delmer, Alain, Dupuis, Jehan, Dilhuydy, Marie, Ferrant, Emmanuelle, Feugier, Pierre, Genevieve, Franck, de Guibert, Sophie, Guieze, Romain, Leblond, Véronique, Levy, Vincent, Leprêtre, Stephane, Merabet, Fatiha, Michallet, Anne-Sophie, Nguyen-Khac, Florence, Quinquenel, Anne, Raynaud, Sophie, Re, Daniel, Thieblemont, Catherine, Tournillhac, Olivier, Troussard, Xavier, Truchan-Graczyk, Malgorzata, Willems, Lise, Ysebaert, Loic, Zini, Jean-Marc, Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Service d'Hématologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie Biologique [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Hématologie biologique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département d'Oncologie Génétique [Rouen] (CLCC Henri Becquerel), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Laboratoire Bio-Santis, Cavaillon, France, Laboratoire d'oncobiologie [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Génétique Médicale (CHU de Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Génétique Chromosomique et Moléculaire [CHU Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'hématologie biologique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pontchaillou [Rennes], Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hématologie Cellulaire [Hospices civils de Lyon], Hospices Civils de Lyon, Lyon, France, Hospices Civils de Lyon (HCL), Service de Cytogénétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Mort cellulaire programmée et résistance aux drogues dans les hémopathies malignes = Cell death and Drug Resistance in Hematological Disorders [CRC], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Uppsala University, French Innovative Leukemia Organization (Filo), Cancéropole Ille de France. Grant Number: 2019-1-EMERG-22-INSERM 6-1, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), and Gestionnaire, Hal Sorbonne Université
- Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Mutation ,Humans ,Chlorambucil ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Hematology ,Tumor Suppressor Protein p53 ,Codon ,Leukemia, Lymphocytic, Chronic, B-Cell ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2022
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