10 results on '"Mugneret, F"'
Search Results
2. Cytogenetic Abnormalities in B-CLL at Binet Stage A: Overview in a Cohort of 484 Untreated Patients and Relations with the ZAP-70 and IgVH Mutation Status.
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Nguyen-Khac, Florence, primary, Bauchu, E. Callet, primary, Bastard, C., primary, Lefebvre, C., primary, Ramond, S., primary, Mugneret, F., primary, Eclache, V., primary, Bergoin, E., primary, Lafage-Pochilatoff, M., primary, Naghib, D., primary, Quilichini, B., primary, Barin, C., primary, Davi, F., primary, Merle-Beral, H., primary, and Raynaud, S. Dominique, primary
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- 2005
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3. Dismal prognostic value of monosomal karyotype in elderly patients with acute myeloid leukemia: a GOELAMS study of 186 patients with unfavorable cytogenetic abnormalities.
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Perrot A, Luquet I, Pigneux A, Mugneret F, Delaunay J, Harousseau JL, Barin C, Cahn JY, Guardiola P, Himberlin C, Recher C, Vey N, Lioure B, Ojeda-Uribe M, Fegueux N, Berthou C, Randriamalala E, Béné MC, Ifrah N, and Witz F
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- Aged, Female, Genetic Predisposition to Disease epidemiology, Genetic Predisposition to Disease genetics, Humans, Incidence, Male, Middle Aged, Multivariate Analysis, Prognosis, Retrospective Studies, Risk Factors, Chromosome Aberrations statistics & numerical data, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Monosomy genetics
- Abstract
The prognosis of acute myeloid leukemia (AML) is very poor in elderly patients, especially in those classically defined as having unfavorable cytogenetics. The recent monosomal karyotype (MK) entity, defined as 2 or more autosomal monosomies or combination of 1 monosomy with structural abnormalities, has been reported to be associated with a worse outcome than the traditional complex karyotype (CK). In this retrospective study of 186 AML patients older than 60 years, the prognostic influence of MK was used to further stratify elderly patients with unfavorable cytogenetics. CK was observed in 129 patients (69%), and 110 exhibited abnormalities according to the definition of MK (59%). MK(+) patients had a complete response rate significantly lower than MK(-) patients: 37% vs 64% (P = .0008), and their 2-year overall survival was also decreased at 7% vs 22% (P < .0001). In multivariate analysis, MK appeared as the major independent prognostic factor related to complete remission achievement (odds ratio = 2.3; 95% confidence interval, 1-5.4, P = .05) and survival (hazard ratio = 1.7; 95% confidence interval, 1.1-2.5, P = .008). In the subgroup of 129 CK(+) patients, survival was dramatically decreased for MK(+) patients (8% vs 28% at P = .03). These results demonstrate that MK is a major independent factor of very poor prognosis in elderly AML.
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- 2011
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4. 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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5. Quinine as a multidrug resistance inhibitor: a phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia.
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Solary E, Drenou B, Campos L, de Crémoux P, Mugneret F, Moreau P, Lioure B, Falkenrodt A, Witz B, Bernard M, Hunault-Berger M, Delain M, Fernandes J, Mounier C, Guilhot F, Garnache F, Berthou C, Kara-Slimane F, and Harousseau JL
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- ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism, Adolescent, Adult, Cytarabine administration & dosage, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Drug Synergism, Drug Therapy, Combination, Female, Humans, Leukemia, Myeloid, Acute metabolism, Male, Middle Aged, Mitoxantrone administration & dosage, Prospective Studies, Quinine administration & dosage, Rhodamine 123 pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Myeloid, Acute drug therapy, Quinine therapeutic use
- Abstract
Based on our previous demonstration that quinine could be used clinically to reverse P-glycoprotein-mediated resistance, we designed a multicenter, randomized trial aiming to determine whether quinine would improve the survival of adult patients (15-60 years old) with de novo acute myelogenous leukemia (AML). These patients randomly received (n = 213) or did not receive (n = 212) a 30 mg/kg/day continuous intravenous infusion of quinine in combination with induction chemotherapy combining idarubicine and cytarabine and, depending on bone marrow examination at day 20, an additional course of cytarabine and mitoxantrone. The mean steady-state quinine concentration was 7.8 mg/L and the mean multidrug resistance reversing activity of serum was 1.96. Complete remission (CR) was obtained in 344 patients (80.9%) without significant influence of quinine. Of the patients in complete remission, 82 were assigned to receive HLA-matched bone marrow transplants, whereas 262 were assigned to 2 courses of intensive consolidation chemotherapy, with or without quinine, depending on initial randomization. The 4-year actuarial overall survival (OS) of the 425 eligible patients was 42.0% +/- 2.5%, without significant influence of quinine. Of 160 patients who could be studied, 54 demonstrated rhodamine 123 efflux. In these patients, quinine significantly improved the CR rate from 12 of 25 (48.0%) to 24 of 29 (82.8%) (P =.01). However, there was no significant difference in OS. Neither mdr1 gene nor P-glycoprotein expression influenced the outcome. We conclude that quinine does not improve the survival of adult patients with de novo AML, even though it improves CR rate in a small subgroup of patients defined by rhodamine 123 efflux.
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- 2003
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6. Prognosis of inv(16)/t(16;16) acute myeloid leukemia (AML): a survey of 110 cases from the French AML Intergroup.
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Delaunay J, Vey N, Leblanc T, Fenaux P, Rigal-Huguet F, Witz F, Lamy T, Auvrignon A, Blaise D, Pigneux A, Mugneret F, Bastard C, Dastugue N, Van den Akker J, Fière D, Reiffers J, Castaigne S, Leverger G, Harousseau JL, and Dombret H
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- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Child, Preschool, Clinical Trials as Topic, Cytarabine administration & dosage, Daunorubicin administration & dosage, Disease-Free Survival, Female, France epidemiology, Humans, Idarubicin administration & dosage, Infant, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Leukemia, Myelomonocytic, Acute genetics, Life Tables, Male, Middle Aged, Mitoxantrone administration & dosage, Multicenter Studies as Topic, Prognosis, Randomized Controlled Trials as Topic, Remission Induction, Retrospective Studies, Risk Factors, Survival Analysis, Treatment Outcome, Chromosome Inversion, Chromosomes, Human, Pair 16 ultrastructure, Daunorubicin analogs & derivatives, Leukemia, Myelomonocytic, Acute mortality
- Abstract
Acute myeloid leukemias (AMLs) carrying inv(16)/t(16;16) chromosomal abnormalities are associated with a good prognosis. However, studies of this AML subtype have been hampered by the few number of patients reported, frequently collectively considered with those with AML carrying the t(8;21) translocation. We performed a retrospective study in 110 patients with inv(16)/t(16;16) AML (median age, 34 years) prospectively enrolled in 6 trials conducted in France between 1987 and 1998, with the aim to investigate prognostic factors for complete remission (CR) achievement and outcome of CR patients in this AML subtype. CR rate was 93%. Bad-prognosis factors for CR achievement were higher white blood cell count (WBC) and lower platelet count (optimal cutpoints at 120 and 30 x 109/L, respectively). At 3 years, estimated overall survival, disease-free survival (DFS), and cumulative incidence of relapse were 58%, 48%, and 42%, respectively. In multivariate analysis, (1) advanced age (optimal cutpoint, 35 years) was the only factor for shorter DFS and (2) advanced age and low platelet count were the 2 factors for shorter survival of CR patients. Outcome of CR patients (1) was not influenced by WBC and cytogenetic findings and (2) was similar among patients allocated to receive allogeneic transplantation, high-dose, or intermediate-dose cytarabine. Interestingly, advanced age was associated with a trend for more frequent additional chromosome abnormalities and predictive of higher cumulative incidence of relapse rather than death in first CR. These results markedly contrast with those reported in patients with t(8;21) AML in whom WBC, and not age, was the main high-risk factor for relapse, DFS, and survival.
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- 2003
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7. M0 AML, clinical and biologic features of the disease, including AML1 gene mutations: a report of 59 cases by the Groupe Français d'Hématologie Cellulaire (GFHC) and the Groupe Français de Cytogénétique Hématologique (GFCH).
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Roumier C, Eclache V, Imbert M, Davi F, MacIntyre E, Garand R, Talmant P, Lepelley P, Lai JL, Casasnovas O, Maynadie M, Mugneret F, Bilhou-Naberra C, Valensi F, Radford I, Mozziconacci MJ, Arnoulet C, Duchayne E, Dastugue N, Cornillet P, Daliphard S, Garnache F, Boudjerra N, Jouault H, Fenneteau O, Pedron B, Berger R, Flandrin G, Fenaux P, and Preudhomme C
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- Adult, Aged, Aged, 80 and over, Bone Marrow pathology, Core Binding Factor Alpha 2 Subunit, Gene Rearrangement, T-Lymphocyte, Humans, Immunoglobulin Heavy Chains genetics, Immunophenotyping, In Situ Hybridization, Fluorescence, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute pathology, Leukocyte Count, Middle Aged, Prognosis, Proto-Oncogene Proteins genetics, Receptor Protein-Tyrosine Kinases genetics, Receptors, Antigen, T-Cell genetics, Retrospective Studies, Survival Rate, fms-Like Tyrosine Kinase 3, DNA-Binding Proteins genetics, Leukemia, Myeloid, Acute genetics, Point Mutation, Transcription Factors genetics
- Abstract
Mutations of the AML1 gene are frequent molecular abnormalities in minimally differentiated acute myeloblastic leukemia (M0 AML), a rare type of AML. In this retrospective multicenter study, morphologic, immunophenotypical, cytogenetic, and molecular features of 59 de novo M0 AML cases were analyzed and correlated to AML1 mutations. Point mutations of AML1 gene were observed in 16 cases (27%). They were correlated with higher white blood cell (WBC) count (P =.001), greater marrow blast involvement (P =.03), higher incidence of immunoglobulin H/T-cell receptor (IgH/TCR) gene rearrangement (P <.0001), and with a borderline significant lower incidence of complex karyotypes. In the 59 patients, FLT3 mutations were the only significant prognostic factors associated with short survival.
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- 2003
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8. Endogenous retroviral sequence is fused to FGFR1 kinase in the 8p12 stem-cell myeloproliferative disorder with t(8;19)(p12;q13.3).
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Guasch G, Popovici C, Mugneret F, Chaffanet M, Pontarotti P, Birnbaum D, and Pébusque MJ
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- 3' Flanking Region, 5' Flanking Region, Cloning, Molecular, Cytogenetic Analysis, Humans, Receptor, Fibroblast Growth Factor, Type 1, Terminal Repeat Sequences, Chromosomes, Human, Pair 19, Chromosomes, Human, Pair 8, Endogenous Retroviruses genetics, Myeloproliferative Disorders genetics, Oncogene Proteins, Fusion genetics, Receptor Protein-Tyrosine Kinases genetics, Receptors, Fibroblast Growth Factor genetics, Translocation, Genetic
- Abstract
FGFR1, a transmembrane receptor tyrosine kinase for fibroblast growth factors, is constitutively activated by chromosomal translocations in an atypical stem-cell myeloproliferative disorder. The FGFR1 tyrosine domain is fused to dimerization domains encoded by 4 alternative genes: FOP at 6q27, CEP110 at 9q33, FIM/ZNF198 at 13q12, and BCR at 22q11. In this study, we report the molecular cloning of the t(8;19)(p12;q13.3), the fifth translocation associated with this syndrome. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and fluorescence in situ hybridization (FISH) demonstrated that the translocation resulted in a long terminal repeat of human endogenous retrovirus gene (HERV-K)/fibroblast growth factor receptor 1 (FGFR1) fusion transcript that incorporated 5' sequences from HERV-K fused in frame to 3' FGFR1 sequences encoding the kinase domain. RT-PCR detected only 1 of the 2 possible fusion transcripts, HERV-K/FGFR1.
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- 2003
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9. Cytogenetic profile of childhood and adult megakaryoblastic leukemia (M7): a study of the Groupe Français de Cytogénétique Hématologique (GFCH).
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Dastugue N, Lafage-Pochitaloff M, Pagès MP, Radford I, Bastard C, Talmant P, Mozziconacci MJ, Léonard C, Bilhou-Nabéra C, Cabrol C, Capodano AM, Cornillet-Lefebvre P, Lessard M, Mugneret F, Pérot C, Taviaux S, Fenneteaux O, Duchayne E, and Berger R
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- Adult, Aged, Child, Child, Preschool, Chromosome Aberrations, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 16, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 21, Female, Humans, Immunophenotyping, Infant, Leukemia, Megakaryoblastic, Acute immunology, Leukemia, Megakaryoblastic, Acute pathology, Male, Middle Aged, Neoplasms, Second Primary, Retrospective Studies, Cytogenetic Analysis, Leukemia, Megakaryoblastic, Acute genetics
- Abstract
To draw the cytogenetic profile of childhood and adult acute megakaryoblastic leukemia (M7), the Groupe Français de Cytogénétique Hématologique collected 53 cases of M7 (30 children and 23 adults). Compared to other acute myeloid leukemias, M7 is characterized by a higher incidence of abnormalities, a higher complexity of karyotypes, and a different distribution of abnormalities among children and adults. Nine cytogenetic groups were identified: normal karyotypes (group 1), patients with Down syndrome (group 2), numerical abnormalities only (group 3), t(1;22)(p13;q13) or OTT-MAL transcript (group 4), t(9;22)(q34;q11) (group 5), 3q21q26 (group 6), -5/del(5q) or -7/del(7q) or both (group 7), i(12)(p10) (group 8), and other structural changes (group 9). Groups 1, 2, 3, and 4 were exclusively composed of children (except one adult in group 3), whereas groups 5, 6, 7, and 8 were mainly made up of adults. The main clinical and hematologic features of these groups were described. No new recurrent abnormality was identified, but mapping of all breakpoints allowed us to specify several possible hot spots of rearrangement: 17q22-23, 11q14-21, 21q21-22, and 16q21-22-23. Although 90.5% of cases had no documented antecedent hematologic disorder or exposure to chemotherapy or radiotherapy, the morphologic and the cytogenetic findings indicated that M7 might be a secondary leukemia more often than suggested by preceding history, particularly among adults. The concurrent analyses of morphologic and cytogenetic data also led us to assume that the initial precursor involved might be more immature in adult than in childhood M7.
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- 2002
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10. CD4(+), CD56(+) DC2 acute leukemia is characterized by recurrent clonal chromosomal changes affecting 6 major targets: a study of 21 cases by the Groupe Français de Cytogénétique Hématologique.
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Leroux D, Mugneret F, Callanan M, Radford-Weiss I, Dastugue N, Feuillard J, Le Mée F, Plessis G, Talmant P, Gachard N, Uettwiller F, Pages MP, Mozziconacci MJ, Eclache V, Sibille C, Avet-Loiseau H, and Lafage-Pochitaloff M
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- Acute Disease, Adolescent, Aged, Aged, 80 and over, Child, Female, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Leukemia immunology, Male, Middle Aged, CD4 Antigens analysis, CD56 Antigen analysis, Chromosome Aberrations, Leukemia genetics
- Abstract
CD4(+), CD56(+) DC2 malignancies constitute a novel disease entity, which has recently been shown to arise from a transformed lymphoid-related plasmacytoid dendritic cell (DC2). Diagnosis is primarily based on a particular immunophenotype with tumor cells expressing CD4 and CD56 antigens in the absence of common lymphoid or myeloid lineage markers. Little is currently known about the cytogenetic features of this disease entity. In this setting, the Groupe Français de Cytogénétique Hématologique (GFCH) initiated a cytogenetic study of 18 adults and 3 children with CD4(+), CD56(+) DC2 acute leukemia using conventional and fluorescence in situ hybridization/24-color karyotyping. Clonal, mostly complex chromosome aberrations were found in 14 patients (66%). Six major recurrent chromosomal targets were defined. These were 5q, 12p, 13q, 6q, 15q, and 9, which were involved in 72% (5q), 64% (12p and 13q), 50% (6q), 43% (15q), and 28% (monosomy 9) of cases, respectively. Cytogenetic features can be summarized as follows: (1) gross genomic imbalances (mostly losses) predominate, (2) no single anomaly can be considered as specific, whereas their combination/accumulation is, and (3) both lymphoid and myeloid lineage-associated rearrangements are observed in unusual combinations in the same cell. This is suggestive of complex multistep tumorigenic mechanisms and is supportive of the hypothesis that CD4(+), CD56(+) DC2 acute leukemia may arise from an undifferentiated nonmyeloid nonlymphoid progenitor cell. In conclusion, the present study documents for the first time the existence of a characteristic cytogenetic profile for this novel disease entity.
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- 2002
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