Marie-Joelle Mozziconacci

Publications (26)147.24 Total impact

• Article: Lenalidomide treatment for patients with myelodysplastic syndrom and low blast count acute myeloid leukemia after azacitidine failure.

  Thomas Prebet, Aude Charbonnier, Véronique Gelsi-Boyer, Marie Joelle Mozziconacci, Didier Blaise, Norbert Vey
  Leukemia & lymphoma 10/2012; · 2.40 Impact Factor
• Article: Molecular similarity between myelodysplastic form of chronic myelomonocytic leukemia and refractory anemia with ring sideroblasts.

  Veronique Gelsi-Boyer, Nathalie Cervera, Francois Bertucci, Mandy Brecqueville, Pascal Finetti, Anne Murati, Christine Arnoulet, Marie-Joelle Mozziconacci, Ken Mills, Nicholas C P Cross, Norbert Vey, Daniel Birnbaum
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  ABSTRACT: Background. Chronic myelomonocytic leukemia is close to, but separate from both myeloproliferative neoplasms and myelodysplastic syndromes, and shows either myeloproliferative or myelodysplastic features. We ask whether this distinction may have a molecular basis. Design and Methods. We established the gene expression profiles of 39 samples of chronic myelomonocytic leukemia (including 12 CD34-positive) and 32 CD34-positive samples of myelodysplastic syndromes by using Affymetrix microarrays, and studied the status of 18 genes by Sanger sequencing and array-comparative genomic hybridization in 53 samples. Results. Analysis of 12 mRNAS from chronic myelomonocytic leukemia established a gene expression signature of 122 probe sets differentially expressed between proliferative and dysplastic cases of chronic myelomonocytic leukemia. As compared to the former, the latter overexpressed genes involved in red blood cell biology. When applied to 32 myelodysplastic syndromes this gene expression signature was able to discriminate refractory anemias with ring sideroblasts from refractory anemias with excess of blasts. By comparing mRNAS from these two forms of myelodysplastic syndromes we derived a second gene expression signature. This signature separated the myelodysplastic and myeloproliferative forms of chronic myelomonocytic leukemias. These results were validated by using two independent gene expression data sets. We found that myelodysplastic chronic myelomonocytic leukemias are characterized by mutations in transcription/epigenetic regulators (ASXL1, RUNX1, TET2) and splicing genes (SRSF2) and the absence of mutations in signaling genes. Conclusions. Myelodysplastic chronic myelomonocytic leukemias and refractory anemias with ring sideroblasts share a common expression program suggesting they are part of a continuum, which is not totally explained by their similar but not identical mutation spectrum.
  Haematologica 10/2012; · 6.42 Impact Factor
• Article: Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenstrom macroglobulinemia.

  Florence Nguyen-Khac, Jerome Lambert, Elise Chapiro, Aurore Grelier, Sarah Mould, Carole Barin, Agnes Daudignon, Nathalie Gachard, Stephanie Struski, Catherine Henry, [......], Jean Chiesa, Marie-Joelle Mozziconacci, Evelyne Callet-Bauchu, Lauren Veronese, Helene Blons, Roger Owen, Julie Lejeune, Sylvie Chevret, Helene Merle-Beral, Veronique Leblond
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  ABSTRACT: Background. Waldenström macroglobulinemia is a mature B-cell disease, the genetic bases of which are poorly understood. Few recurrent chromosomal abnormalities have been reported, and their prognostic value is not known. Design and Methods. We conducted a prospective cytogenetic study of Waldenström macroglobulinemia and examined the prognostic value of chromosomal aberrations in an international randomised trial. Results. 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%). Trisomy of chromosomes 4 and 18 were significantly associated. Translocation involving IGH genes was 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 (PFS) and short disease-free survival (DFS). Although rare (<5%), trisomy 12 was associated with short PFS. Conclusions. The cytogenetic profile of Waldenström macroglobulinemia thus 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. The trial is registered with Clinicaltrials.gov, numbers NCT00566332 and NCT00608374.
  Haematologica 10/2012; · 6.42 Impact Factor
• Article: Incidence of 17p deletions and TP53 mutation in myelodysplastic syndrome and acute myeloid leukemia with 5q deletion.

  Amel Sebaa, Lionel Ades, Fanny Baran-Marzack, Marie-Joelle Mozziconacci, Dominique Penther, Sophie Dobbelstein, Aspasia Stamatoullas, Christian Récher, Thomas Prebet, Soraya Moulessehoul, Pierre Fenaux, Virginie Eclache
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  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. © 2012 Wiley Periodicals, Inc.
  Genes Chromosomes and Cancer 08/2012; 51(12):1086-92. · 3.31 Impact Factor
• Article: PICALM-MLLT10 acute myeloid leukemia: A French cohort of 18 patients.

  Cecile Borel, Nicole Dastugue, Valérie Cances-Lauwers, Marie-Joelle Mozziconacci, Thomas Prebet, Norbert Vey, Aranud Pigneux, Eric Lippert, Sorin Visanica, Faezeh Legrand, Jean Philippe Rault, Sylvie Taviaux, Christian Bastard, Francine Mugneret, Marie Agnes Collonges Rames, Nathalie Gachard, Pascaline Talmant, Eric Delabesse, Christian Récher
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  ABSTRACT: The PICALM-MLLT10 fusion gene, generated by the t(10;11)(p12-13;q14-21) translocation, is a rare but recurrent event in acute leukemias. In this study, we assessed the characteristics and outcome of 18 PICALM-MLLT10 AML patients. As compared with non PICALM-MLLT10 patients (n=72), PICALM-MLLT10 AML were characterized by more frequent extramedullary diseases, CD7 expression and higher platelet counts. Three out of four therapy-related PICALM-MLLT10 AMLs had been previously treated for diffuse large B-cell lymphoma. The complete response rate was 71% after intensive chemotherapy. PICALM-MLLT10 patients had a shorter median overall survival than patients with favorable cytogenetics (12months vs. not reached, p=0.07) but not significantly different from those of intermediate (26months, p=0.32) or unfavorable cytogenetic groups (8months, p=0.13). Long term responses were achieved in a subset of patients after allogeneic stem-cell transplantation but also after high-dose cytarabine.
  Leukemia research 08/2012; 36(11):1365-9. · 2.36 Impact Factor
• Article: Mutation analysis of ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 in myeloproliferative neoplasms.

  Mandy Brecqueville, Jérôme Rey, François Bertucci, Emilie Coppin, Pascal Finetti, Nadine Carbuccia, Nathalie Cervera, Véronique Gelsi-Boyer, Christine Arnoulet, Olivier Gisserot, Denis Verrot, Borhane Slama, Norbert Vey, Marie-Joelle Mozziconacci, Daniel Birnbaum, Anne Murati
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  ABSTRACT: Since the discovery of the JAK2V617F tyrosine kinase-activating mutation several genes have been found mutated in nonchronic myeloid leukemia (CML) myeloproliferative neoplasms (MPNs), which mainly comprise three subtypes of "classic" MPNs; polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). We searched for mutations in ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 genes in 149 non-CML MPNs, including 127 "classic" MPNs cases. JAK2 was mutated in 100% PV, 66% ET and 68% MF. We found a high incidence of ASXL1 mutation in MF patients (20%) and a low incidence in PV (7%) and ET (4%) patients. Mutations in the other genes were rare (CBL, DNMT3A, IDH2, MPL, SF3B1, SUZ12, NF1) or absent (IDH1).
  Genes Chromosomes and Cancer 04/2012; 51(8):743-55. · 3.31 Impact Factor
• Source

  Available from: PubMed Central

  Article: Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases.

  Véronique Gelsi-Boyer, Mandy Brecqueville, Raynier Devillier, Anne Murati, Marie-Joelle Mozziconacci, Daniel Birnbaum
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  ABSTRACT: The ASXL1 gene is one of the most frequently mutated genes in malignant myeloid diseases. The ASXL1 protein belongs to protein complexes involved in the epigenetic regulation of gene expression. ASXL1 mutations are found in myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). They are generally associated with signs of aggressiveness and poor clinical outcome. Because of this, a systematic determination of ASXL1 mutational status in myeloid malignancies should help in prognosis assessment.
  Journal of Hematology & Oncology 03/2012; 5:12. · 3.99 Impact Factor
• Article: Low-dose Nilotinib can maintain complete molecular remissions in FIP1L1/PDGFRA-positive hypereosinophilic syndrome.

  Emeline Tabouret, Aude Charbonnier, Marie-Joelle Mozziconacci, Vadim Ivanov
  Leukemia research 01/2011; 35(1):136. · 2.36 Impact Factor
• Article: Chromosomal abnormalities in transformed Ph-negative myeloproliferative neoplasms are associated to the transformation subtype and independent of JAK2 and the TET2 mutations.

  Florence Nguyen-Khac, Claude Lesty, Virginie Eclache, Lucile Couronné, Olivier Kosmider, Joris Andrieux, Marie-Agnes Collonge-Rame, Dominique Penther, Marina Lafage, Chrystele Bilhou-Nabera, Elise Chapiro, Marie-Joelle Mozziconacci, Francine Mugneret, Nathalie Gachard, Nathalie Nadal, Eric Lippert, Stephanie Struski, Nicole Dastugue, Christine Cabrol, Olivier A Bernard
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  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.
  Genes Chromosomes and Cancer 10/2010; 49(10):919-27. · 3.31 Impact Factor
• Article: Loss of the Y chromosome in Philadelphia-positive cells predicts a poor response of chronic myeloid leukemia patients to imatinib mesylate therapy.

  Eric Lippert, Gabriel Etienne, Marie-Joelle Mozziconacci, Sophy Laibe, Carine Gervais, Stéphane Girault, Nathalie Gachard, Isabelle Tigaud, Nicole Dastugue, François Huguet, Marie-Pierre Fort, Laurence Legros, Virginie Eclache, Francois-Xavier Mahon
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  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.
  Haematologica 09/2010; 95(9):1604-7. · 6.42 Impact Factor
• Article: Alteration of cohesin genes in myeloid diseases.

  Julien Rocquain, Véronique Gelsi-Boyer, José Adélaïde, Anne Murati, Nadine Carbuccia, Norbert Vey, Daniel Birnbaum, Marie-Joelle Mozziconacci, Max Chaffanet
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  ABSTRACT: New genes involved in leukemogenesis, such as ASXL1 and TET2, have been identified recently using genomic analyses of DNA from patient samples. We have studied by array-comparative genomic hybridization (aCGH) a series of 167 samples including myelodysplastic syndromes, chronic myelomonocytic leukemias, and acute myeloid leukemias. We found a deletion of the RAD21 and STAG2 genes, which encode two components of the cohesin complex. We propose that these alterations may compromise the cohesin complex and its regulation of the transcription of genes.
  American Journal of Hematology 09/2010; 85(9):717-9. · 4.67 Impact Factor
• Article: Absence of R140Q mutation of isocitrate dehydrogenase 2 in gliomas and breast cancers.

  Stéphane Raynaud, Nadine Carbuccia, Carole Colin, José Adélaïde, Marie-Joelle Mozziconacci, Philippe Metellus, Olivier Chinot, Daniel Birnbaum, Max Chaffanet, Dominique Figarella-Branger
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  ABSTRACT: Somatic mutations of isocitrate dehydrogenase (IDH)-1 and IDH2 proteins have been described in gliomas. The mutations target the R132 amino acid residue and the R172 residue in IDH1 and IDH2, respectively. The same mutations were observed in acute myeloid leukemias with normal karyotype, but a new mutation in IDH2 (R140Q substitution) was detected in malignant myeloid diseases and appears to be the most frequent IDH mutation in these pathologies. To the best of our knowledge, no study thus far has reported the presence of this R140Q mutation in IDH2 in tumors of the nervous system and breast cancers. We evaluated IDH1 and IDH2 exon 4 in 48 low-grade gliomas, 58 primary glioblastomas and 94 breast cancers to evaluate the frequency of mutation and investigated the R140Q substitution in IDH2. The results were compared to our recently obtained results in hematopoietic diseases. The frequency of IDH1 and IDH2 mutations in our panel of gliomas was similar to previously reported mutations. No IDH2 R140 mutation was observed. Compared to hematopoietic diseases, the IDH2 R172 mutation was also more rare and IDH1 mutations more prominent in tumors of the nervous system. No IDH1 or IDH2 mutation was detected in the 94 breast cancer samples. Thus, the IDH2 R140 mutation appears to be restricted to hematopoietic diseases.
  Oncology letters 09/2010; 1(5):883-884. · 0.11 Impact Factor
• Source

  Available from: PubMed Central

  Article: Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias.

  Julien Rocquain, Nadine Carbuccia, Virginie Trouplin, Stéphane Raynaud, Anne Murati, Meyer Nezri, Zoulika Tadrist, Sylviane Olschwang, Norbert Vey, Daniel Birnbaum, Véronique Gelsi-Boyer, Marie-Joelle Mozziconacci
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  ABSTRACT: Gene mutation is an important mechanism of myeloid leukemogenesis. However, the number and combination of gene mutated in myeloid malignancies is still a matter of investigation. We searched for mutations in the ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in 65 myelodysplastic syndromes (MDSs) and 64 acute myeloid leukemias (AMLs) without balanced translocation or complex karyotype. Mutations in ASXL1 and CBL were frequent in refractory anemia with excess of blasts. Mutations in TET2 occurred with similar frequency in MDSs and AMLs and associated equally with either ASXL1 or NPM1 mutations. Mutations of RUNX1 were mutually exclusive with TET2 and combined with ASXL1 but not with NPM1. Mutations in FLT3 (mutation and internal tandem duplication), IDH1, IDH2, NPM1 and WT1 occurred primarily in AMLs. Only 14% MDSs but half AMLs had at least two mutations in the genes studied. Based on the observed combinations and exclusions we classified the 12 genes into four classes and propose a highly speculative model that at least a mutation in one of each class is necessary for developing AML with simple or normal karyotype.
  BMC Cancer 01/2010; 10:401. · 3.01 Impact Factor
• Article: High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder.

  Claude Preudhomme, Aline Renneville, Violaine Bourdon, Nathalie Philippe, Catherine Roche-Lestienne, Nicolas Boissel, Nathalie Dhedin, Jean-Marie André, Pascale Cornillet-Lefebvre, André Baruchel, Marie-Joelle Mozziconacci, Hagay Sobol
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  ABSTRACT: Familial platelet disorder (FPD), a rare autosomal dominant disorder characterized by quantitative and qualitative platelet abnormalities, is considered as a model of genetic predisposition to acute myeloid leukemia (AML). So far, monoallelic RUNX1 germline mutations have been found in 19 of 20 families with reported FPD, and the analysis of blast cells from only 5 patients at acute leukemia (AL) stage has shown no additional RUNX1 abnormality. Here, we performed RUNX1 analysis at constitutional and somatic levels in 8 persons with FPD who developed AL from 4 independent families. In addition to the germline RUNX1 mutation, we identified a second RUNX1 alteration in 6 AML cases (acquired point mutations in 4 cases and duplication of the altered RUNX1 allele associated with acquired trisomy 21 in 2 other cases). Although haploinsufficiency of RUNX1 causes FPD, our findings suggest that a second genetic event involving RUNX1 is often associated with progression to AML.
  Blood 05/2009; 113(22):5583-7. · 9.90 Impact Factor
• Article: Presence of a minor Philadelphia-positive clone in young adults with de novo T-cell ALL.

  Thomas Prebet, Marie Joelle Mozziconacci, Danielle Sainty, Christine Arnoulet, Marina Lafage, Nicole Dastugue, Aude Charbonnier, Diane Coso, Jean-Albert Gastaut, Didier Blaise, Norbert Vey
  Leukemia & lymphoma 03/2009; 50(3):485-7. · 2.40 Impact Factor
• Source

  Available from: José Adélaide

  Article: Genome profiling of chronic myelomonocytic leukemia: frequent alterations of RAS and RUNX1 genes.

  Véronique Gelsi-Boyer, Virginie Trouplin, José Adélaïde, Nicola Aceto, Virginie Remy, Stephane Pinson, Claude Houdayer, Christine Arnoulet, Danielle Sainty, Mohamed Bentires-Alj, Sylviane Olschwang, Norbert Vey, Marie-Joëlle Mozziconacci, Daniel Birnbaum, Max Chaffanet
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  ABSTRACT: Chronic myelomonocytic leukemia (CMML) is a hematological disease close to, but separate from both myeloproliferative disorders (MPD) and myelodysplastic syndromes and may show either myeloproliferative (MP-CMML) or myelodysplastic (MD-CMML) features. Not much is known about the molecular biology of this disease. We studied a series of 30 CMML samples (13 MP- and 11 MD-CMMLs, and 6 acutely transformed cases) from 29 patients by using Agilent high density array-comparative genomic hybridization (aCGH) and sequencing of 12 candidate genes. Two-thirds of samples did not show any obvious alteration of aCGH profiles. In one-third we observed chromosome abnormalities (e.g. trisomy 8, del20q) and gain or loss of genes (e.g. NF1, RB1 and CDK6). RAS mutations were detected in 4 cases (including an uncommon codon 146 mutation in KRAS) and PTPN11 mutations in 3 cases. We detected 11 RUNX1 alterations (9 mutations and 2 rearrangements). The rearrangements were a new, cryptic inversion of chromosomal region 21q21-22 leading to break and fusion of RUNX1 to USP16. RAS and RUNX1 alterations were not mutually exclusive. RAS pathway mutations occurred in MP-CMMLs (approximately 46%) but not in MD-CMMLs. RUNX1 alterations (mutations and cryptic rearrangement) occurred in both MP and MD classes (~38%). We detected RAS pathway mutations and RUNX1 alterations. The latter included a new cryptic USP16-RUNX1 fusion. In some samples, two alterations coexisted already at this early chronic stage.
  BMC Cancer 11/2008; 8:299. · 3.01 Impact Factor
• Article: A fifteen-year cytogenetic remission following interferon treatment in a patient with an indolent ETV6-ABL positive myeloproliferative syndrome.

  Marie-Joelle Mozziconacci, Danielle Sainty, Christian Chabannon
  American Journal of Hematology 08/2007; 82(7):688-9. · 4.67 Impact Factor
• Article: Dual lympho-myeloproliferative disorder in a patient with t(8;22) with BCR-FGFR1 gene fusion.

  Anne Murati, Christine Arnoulet, Marina Lafage-Pochitaloff, José Adélaide, Martine Derré, Borhane Slama, Bénédicte Delaval, Cornel Popovici, Norbert Vey, Luc Xerri, Marie-Joelle Mozziconacci, Olivier Boulat, Danielle Sainty, Daniel Birnbaum, Max Chaffanet
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  ABSTRACT: The case of a patient presenting with a myeloproliferative disorder (MPD) characterized by a t(8;22) (p12;q11) translocation was investigated. The rearrangement resulted in the production of BCR-FGFR1 and FGFR1-BCR chimeric transcripts after in-frame fusions of BCR exon 4 with FGFR1 exon 9 and FGFR1 exon 8 with BCR exon 5, respectively. The four previously reported patients with such translocation presented with an atypical chronic myeloid leukemia (CML) without Philadelphia chromosome. In addition to a myeloproliferation, the patient had a B cell proliferation. The phenotypic characterization of the lymphoid cells in the bone marrow showed a continuum of maturation from blast B cells to polyclonal lymphocytes. In the blood, B cells showed a complete polyclonal maturation. The BCR-FGFR1 gene fusion was detected by dual-color fluorescence in situ hybridization in both CD19- and CD19+ populations. In contrast to the other FGFR1-MPDs that show myeloid and T cell proliferation, we propose that this t(8;22) MPD is a myeloid and B cell disease, and potentially a novel type of hematological disease. Although the FGFR1-MPD is rare, its study provides interesting clues to the understanding of hematopoietic stem cell biology and oncogene activation.
  International Journal of Oncology 07/2005; 26(6):1485-92. · 2.40 Impact Factor
• Article: A report from the LALA-94 and LALA-SA groups on hypodiploidy with 30 to 39 chromosomes and near-triploidy: 2 possible expressions of a sole entity conferring poor prognosis in adult acute lymphoblastic leukemia (ALL).

  Christiane Charrin, Xavier Thomas, Martine Ffrench, Quoc-Hung Le, Joris Andrieux, Marie-Joelle Mozziconacci, Jean-Luc Laï, Chrystele Bilhou-Nabera, Lucienne Michaux, Alain Bernheim, Christian Bastard, Hossein Mossafa, Christine Perot, Odile Maarek, Claude Boucheix, Véronique Lheritier, André Delannoy, Denis Fière, Nicole Dastugue
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  ABSTRACT: To reveal the relationship between hypodiploidy with 30 to 39 chromosomes and near-triploidy in acute lymphoblastic leukemia (ALL), we studied 24 patients presenting with one of these aneuploidies among 623 adults with ALL registered in the Leucemie Aigue Lymphoblastique de l'Adulte (LALA) protocols. The 2 ploidy groups presented a striking similarity of their cytogenetic profiles: chromosomes 2, 3, 4, 7, 13, 15, 16, and 17, significantly monosomic in hypodiploidy 30 to 39, were also frequently disomic in near-triploidy, whereas those retained in pairs in hypodiploidy 30 to 39 were frequently tetrasomic in near-triploidy. DNA content data revealed the simultaneous presence of 2 aneuploid peaks in most tested cases (DNA indexes: 0.72-0.87/1.39-1.89) and a multiple correspondence analysis applied on cytogenetic profiles ascertained their strong relationship. We thus assumed that near-triploidy derives from the duplication of hypodiploidy with 30 to 39 chromosomes and that both aneuploid groups are 2 expressions of the same disease. These 24 patients presented with B-cell phenotype, low leukocytoses (median white blood cell count, 4.2 x 10(9)/L), and poor prognosis (complete remission, 57%; median disease-free-survival, 8 months; median survival, 10.4 months) comparable to that of Ph(+) patients treated according to the same protocol. We suggest that hypodiploidy with 30 to 39 chromosomes or near-triploidy should be regarded as a new high-risk factor in the risk stratification of adult ALL protocols.
  Blood 11/2004; 104(8):2444-51. · 9.90 Impact Factor
• Article: The benefit of induction chemotherapy in patients age > or = 75 years.

  Norbert Vey, Diane Coso, Valerie-Jeanne Bardou, Anne-Marie Stoppa, Anne-Chantal Braud, Reda Bouabdallah, Daniele Sainty, Marie-Joelle Mozziconacci, Marina Lafage, Gandhi Damaj, Didier Blaise, Jean-Albert Gastaut, Dominique Maraninchi
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  ABSTRACT: Patients age > or = 75 years with acute myeloid leukemia (AML) generally are offered palliative treatments instead of induction chemotherapy. The authors conducted a retrospective study comparing the outcomes among these elderly patients with the outcomes among younger patients to assess the impact of intensive treatment approaches in this age group. One hundred ten consecutive patients age > or = 75 years with newly diagnosed AML (excluding patients with acute promyelocytic leukemia) were treated in the authors' center over 10 years. Initial treatment was comprised of anthracycline-based induction chemotherapy (i.e., intravenous idarubicin or daunorubicin for 3 days plus cytarabine [ARAC] for 7 days [3 + 7 regimen] or oral idarubicin) for 62 patients (56%), antimetabolite-based chemotherapy (including low-dose ARAC, oral 6-mercaptopurine plus methotrexate, or hydroxyurea) for 40 patients (36%), and supportive care only for 8 patients (7%). Results were compared with the results from 200 patients ages 65-74 years who were treated during the same period. A complete response (CR) to anthracycline-based induction therapy was achieved by 23 of 62 patients (37%), and the 2-year overall survival rate was 22% (which was not statistically different from the group of patients ages 65-74 years). In a multivariate analysis of the entire study group (310 patients), treatment (anthracycline-based vs. other) and age as continuous variable were found to affect survival significantly. In a Landmark analysis, the achievement of a CR translated into improved survival in patients age > or = 75 years. Patients age > or = 75 years should not be excluded systematically from intensive chemotherapy regimens. Decisions should be based on stratification systems that include functional status and comorbidity assessments as well as prognostic factors, such as cytogenetics.
  Cancer 08/2004; 101(2):325-31. · 4.77 Impact Factor