R Berger

Publications (244)1140.64 Total impact

• Article: The most frequent t(14;19)(q32;q13)-positive B-cell malignancy corresponds to an aggressive subgroup of atypical chronic lymphocytic leukemia.

  E Chapiro, I Radford-Weiss, C Bastard, I Luquet, C Lefebvre, E Callet-Bauchu, D Leroux, P Talmant, M-J Mozziconacci, F Mugneret, [......], S Ramond, C Terré, E Lippert, F Berger, P Felman, H Merle-Béral, O A Bernard, F Davi, R Berger, F Nguyen-Khac
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 06/2008; 22(11):2123-7. · 8.30 Impact Factor
• Article: Hyperdiploid karyotypes in acute myeloid leukemia define a novel entity: a study of 38 patients from the Groupe Francophone de Cytogenetique Hematologique (GFCH).

  I Luquet, J L Laï, C Barin, L Baranger, C Bilhou-Nabera, E Lippert, C Gervais, P Talmant, P Cornillet-Lefebvre, C Perot, [......], H Poirel, I Tigaud, C Cabrol, P Rousselot, S Daliphard, M Imbert, R Garand, F Geneviève, R Berger, C Terre
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  ABSTRACT: A series of 38 patients with acute myeloblastic leukemia (AML) with 49 or more chromosomes and without structural abnormalities was selected within the Groupe Francophone de Cytogénétique Hématologique (GFCH) to better define their characteristics. The median age of the patients was 65 years, and all FAB subtypes were represented. Although all chromosomes were gained, some seems to prevail: chromosome 8 (68%), 21 (47%), 19 (37%), and 13 and 14 (34% each). Since MLL rearrangement leads patients in a group with an unfavorable prognosis, search for cryptic rearrangements of MLL was performed in 34 patients and showed abnormalities in 5 (15%). When we applied the most frequent definition of complex karyotypes (three or more abnormalities), all patients with high hyperdiploid AML fall in the unfavorable category. Among the 18 patients without MLL rearrangement receiving an induction therapy, 16 (89%) reached CR and 6 (33%) were still alive after a 31-month median follow-up (14-61 months). Although this study was retrospective, these results suggest that high hyperdiploid AML without chromosome rearrangement seems to be a subgroup of uncommon AML (less than 1%), and may be better classified in the intermediate prognostic group.
  Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 02/2008; 22(1):132-7. · 8.30 Impact Factor
• Article: Fluorescence in situ hybridization analysis of 110 hematopoietic disorders with chromosome 5 abnormalities: do de novo and therapy-related myelodysplastic syndrome-acute myeloid leukemia actually differ?

  M Lessard, C Hélias, S Struski, N Perrusson, F Uettwiller, M-J Mozziconacci, M Lafage-Pochitaloff, N Dastugue, C Terré, F Brizard, [......], A Herry, I Luquet, F Desangles, L Michaux, C Verellen-Dumoulin, C Perrot, J Van den Akker, J Lespinasse, V Eclache, R Berger
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  ABSTRACT: A retrospective cytogenetic study of acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS) was conducted by the Groupe Francophone de Cytogénétique Hématologique (GFCH) to evaluate the structural abnormalities of chromosome 5 associated with other chromosomal abnormalities, in particular of chromosome 7, in these pathologies. In all, 110 cases of AML/MDS were recruited based on the presence of chromosome 5 abnormalities under conventional cytogenetics and supplemented by a systematic fluorescence in situ hybridization study of chromosomes 5 and 7. The abnormalities of the long arm of chromosome 5 (5q) were deletions of various sizes and sometimes cryptic. The 5q abnormalities were associated with translocations in 54% of cases and were simple deletions in 46%. In 68% of cases, 5q deletions were associated with chromosome 7 abnormalities, and 90% of these presented a complex karyotype. Of the 110 patients, 28 had a hematopoietic disorder secondary to chemotherapy, radiotherapy, or both. Among 82 patients with de novo AML/MDS, 63 were older than 60 years. Chromosomal abnormalities often associated hypodiploidy and chromosome 5 and 7 abnormalities in complex karyotypes, features resembling those of secondary hemopathies. Systematic investigation of the exposure to mutagens and oncogenes is thus essential to specify the factors potentially involved in MDS/AML with 5q abnormalities.
  Cancer Genetics and Cytogenetics 08/2007; 176(1):1-21. · 1.39 Impact Factor
• Article: Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRbeta-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique.

  B Cauwelier, H Cavé, C Gervais, M Lessard, C Barin, C Perot, J Van den Akker, F Mugneret, C Charrin, M P Pagès, [......], N Van Roy, K D Keersmaecker, J Cools, F Sigaux, J Soulier, A Hagemeijer, A D Paepe, N Dastugue, R Berger, F Speleman
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  ABSTRACT: Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRbeta) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCRbeta-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCRbeta-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCRbeta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRbeta-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRbeta-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRbeta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.
  Leukemia 02/2007; 21(1):121-8. · 9.56 Impact Factor
• Article: Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCR-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique

  B Cauwelier, H Cav|[eacute, C Gervais, M Lessard, C Barin, C Perot, J Van den Akker, F Mugneret, C Charrin, M P Pag|[egrave]|s, [......], N Van Roy, K D Keersmaecker, J Cools, F Sigaux, J Soulier, A Hagemeijer, A D Paepe, N Dastugue, R Berger, F Speleman
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  ABSTRACT: Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCR) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCR-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCR-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCR-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCR-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCR-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCR-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.Keywords: TCR-HOXA rearrangement, T-ALL, HOXA10, HOXA10b
  Leukemia 10/2006; 21(1):121-128. · 9.56 Impact Factor
• Article: NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogénétique Hématologique.

  S P Romana, I Radford-Weiss, R Ben Abdelali, C Schluth, A Petit, N Dastugue, P Talmant, C Bilhou-Nabera, F Mugneret, M Lafage-Pochitaloff, [......], C Perot, J Van den Akker, S Fert-Ferrer, C Cabrol, C Charrin, I Tigaud, H Poirel, M Vekemans, O A Bernard, R Berger
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  ABSTRACT: The NUP98 gene is fused with 19 different partner genes in various human hematopoietic malignancies. In order to gain additional clinico-hematological data and to identify new partners of NUP98, the Groupe Francophone de Cytogénétique Hématologique (GFCH) collected cases of hematological malignancies where a 11p15 rearrangement was detected. Fluorescence in situ hybridization (FISH) analysis showed that 35% of these patients (23/66) carried a rearrangement of the NUP98 locus. Genes of the HOXA cluster and the nuclear-receptor set domain (NSD) genes were frequently fused to NUP98, mainly in de novo myeloid malignancies whereas the DDX10 and TOP1 genes were equally rearranged in de novo and in therapy-related myeloid proliferations. Involvement of ADD3 and C6ORF80 genes were detected, respectively, in myeloid disorders and in T-cell acute lymphoblastic leukemia (T-ALL), whereas the RAP1GDS1 gene was fused to NUP98 in T-ALL. Three new chromosomal breakpoints: 3q22.1, 7p15 (in a localization distinct from the HOXA locus) and Xq28 were detected in rearrangements with the NUP98 gene locus. The present study as well as a review of the 73 cases previously reported in the literature allowed us to delineate some chromosomal, clinical and molecular features of patients carrying a NUP98 gene rearrangements.
  Leukemia 05/2006; 20(4):696-706. · 9.56 Impact Factor
• Article: Loss of the NPM1 gene in myeloid disorders with chromosome 5 rearrangements.

  R Berger, M Busson, L Baranger, C Hélias, M Lessard, N Dastugue, F Speleman
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  ABSTRACT: The assignment with chromosome banding techniques of the breakpoints of the recurrent translocation t(3;5) which leads to NPM1/MLF1 gene fusion in myeloid malignancies has not been unequivocal. In order to assess whether this is due to uncertainty in interpretation of the observed banding pattern or whether it reflects true genomic heterogeneity, we decided to analyze the breakpoint positions using fluorescence in situ (FISH) techniques in eight patients with myeloid malignancies and rearrangements of chromosomes 3 and 5. In three patients, colocalization of the NPM1 and MLF1 spanning BACs was demonstrated and NPM1/MLF1 fusion shown by PCR in one while in the remaining cases breakpoints were located outside the NPM1 and MLF1 loci. Interestingly, loss of a copy of the NPM1 gene was found in three of these latter patients. This findings suggest that haploinsufficiency of NPM1 may play a role in subtypes of myelodysplasias and leukemias.
  Leukemia 03/2006; 20(2):319-21. · 9.56 Impact Factor
• Article: Cytogenetic study of 75 erythroleukemias.

  M Lessard, S Struski, V Leymarie, G Flandrin, M Lafage-Pochitaloff, M-J Mozziconacci, P Talmant, C Bastard, C Charrin, L Baranger, C Hélias, P Cornillet-Lefebvre, F Mugneret, C Cabrol, M-P Pagès, D Fert-Ferret, F Nguyen-Khac, B Quilichini, C Barin, R Berger
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  ABSTRACT: Chromosomal abnormalities of erythroleukemia (EL) are often described as complex and unspecific. A retrospective study of 75 EL defined following the WHO classification was performed by the Groupe Francophone de Cytogénétique Hématologique (GFCH) in order to reexamine the cytogenetics of this infrequent leukemia subtype. Clonal chromosomal abnormalities were found in 57 patients (76%), distributed in 4 subgroups according to their ploidy status: pseudodiploid (16%), hypodiploid (47%), hyperdiploid (19%), and 18% mixed cases associating 2 different clones (hypodiploid+hyperdiploid) or (pseudodiploid+hyperdiploid). Complex rearrangements and hypodiploid chromosome number were widely dominant (50%). Partial or entire monosomies represented 56% of abnormalities. Chromosomes 5 and 7 were the most frequently involved (41 and 33 times, respectively), followed by chromosomes 8, 16, and 21 (19 times each). Unbalanced abnormalities were more frequent than balanced. All these kinds of abnormalities were observed in de novo as well as in secondary EL. Four out of 7 cases of "pure erythroid" leukemia were associated with a BCR-ABL fusion. Lastly, no chromosome abnormality specific to EL could be established. However, the large overlap of chromosomal abnormality patterns of EL (pure erythroid form excepted) and refractory anemia with excess of blasts in transformation (RAEB-t) favors the hypothesis of similarities between these 2 hematologic disorders.
  Cancer Genetics and Cytogenetics 01/2006; 163(2):113-22. · 1.39 Impact Factor
• Article: NUP214-ABL1 amplification in t(5;14)/HOX11L2-positive ALL present with several forms and may have a prognostic significance.

  P Ballerini, M Busson, S Fasola, J van den Akker, H Lapillonne, S P Romana, P Marynen, O A Bernard, J Landman-Parker, R Berger
  Leukemia 04/2005; 19(3):468-70. · 9.56 Impact Factor
• Article: Expression of the MN1-TEL fusion protein in the human UCSD/AML1 leukemic cell line.

  V Della Valle, L Guglielmi, M Busson, E C Zwarthoff, R Berger, O A Bernard
  Leukemia 10/2004; 18(9):1558-60. · 9.56 Impact Factor
• Article: t(5;14)/HOX11L2-positive T-cell acute lymphoblastic leukemia. A collaborative study of the Groupe Français de Cytogénétique Hématologique (GFCH).

  R Berger, N Dastugue, M Busson, J Van Den Akker, C Pérot, P Ballerini, A Hagemeijer, L Michaux, C Charrin, M P Pages, [......], C Léonard, F Speleman, B Poppe, C Bastard, S Taviaux, B Quilichini, C Herens, M-J Grégoire, H Cavé, O A Bernard
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  ABSTRACT: To accurately estimate the incidence of HOX11L2 expression, and determine the associated cytogenetic features, in T-cell acute lymphoblastic leukemia (T-ALL), the Groupe Français de Cytogénétique Hématologique (GFCH) carried out a retrospective study of both childhood and adult patients. In total, 364 patients were included (211 children </=15 years and 153 adults), and 67 (18.5%) [47 children (22.4%) and 20 adults (13.1%)] were shown to either harbor the t(5;14)q35;q32) translocation or express the HOX11L2 gene or both. Most of the common hematological parameters did not show significant differences within positive and negative populations, whereas the incidence of CD1a+/CD10+ and cytoplasmic CD3+ patients was significantly higher in positive than in negative children. Out of the 63 positive patients investigated by conventional cytogenetics, 32 exhibited normal karyotype, whereas the others 31 showed clonal chromosome abnormalities, which did not include classical T-ALL specific translocations. Involvement of the RANBP17/HOX11L2 locus was ascertained by fluorescence in situ hybridization in six variant or alternative (three-way translocation or cytogenetic partner other than 14q32) translocations out of the 223 patients. Our results also show that HOX11L2 expression essentially occurs as a result of a 5q35 rearrangement, but is not associated with another identified T-ALL specific recurrent genetic abnormality, such as SIL-TAL fusion or HOX11 expression.
  Leukemia 10/2003; 17(9):1851-7. · 9.56 Impact Factor
• Article: A novel real-time RT-PCR assay for quantification of OTT-MAL fusion transcript reliable for diagnosis of t(1;22) and minimal residual disease (MRD) detection.

  P Ballerini, A Blaise, T Mercher, B Pellegrino, C Perot, J van den Akker, E Gatbois, M Adam, L Douay, R Berger, O Bernard, J Landman-Parker
  Leukemia 07/2003; 17(6):1193-6. · 9.56 Impact Factor
• Article: [Molecular basis of the t(1;22)(p13;q13) specific for human acute megakaryoblastic leukemia].

  T Mercher, G Courtois, R Berger, O A Bernard
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  ABSTRACT: The t(1;22)(p13;q13) translocation is specifically associated with infant acute megakaryoblastic leukemia (M7). We have recently characterized the two genes involved in this translocation: OTT (One Two Two) and MAL (Megakaryoblastic Acute Leukemia) respectively located on chromosome 1 and 22. The t(1;22) translocation results in the fusion of these genes in all the cases studied to date. We summarize here present knowledge regarding this translocation.
  Pathologie Biologie 03/2003; 51(1):27-32. · 1.53 Impact Factor
• Article: Chromosome 21 abnormalities with AML1 amplification in acute lymphoblastic leukemia.

  M Busson-Le Coniat, F Nguyen Khac, M T Daniel, O A Bernard, R Berger
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  ABSTRACT: Fluorescence in situ hybridization (FISH) studies were performed in three cases of acute lymphoblastic leukemia (ALL) with marker chromosomes to analyze the contribution of chromosome 21 in these markers. FISH with a chromosome 21 painting probe confirmed that chromosome 21 was involved in all three cases. FISH with YAC probes showed that the number of extra copies varied according to their location on chromosome 21. Attention was focused on the AML1 gene, which was present as five copies in most of the cells exhibiting the marker chromosomes. As controls, 11 cases of childhood ALL were studied with PAC probes covering AML1. The results agreed with the banded karyotypes in 10 patients. FISH uncovered a clone with four copies of AML1 which were only observed by FISH analysis of interphase nuclei in one patient. No point mutation was detected in exons 3-5, encoding the runt domain of AML1, in the three cases, suggesting an oncogenic role of wild-type AML1 amplification.
  Genes Chromosomes and Cancer 12/2001; 32(3):244-9. · 3.31 Impact Factor
• Article: B-cell acute lymphoblastic leukemia with tandem t(14;14)(q11;q32).

  R Berger, M Busson, M T Daniel
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  ABSTRACT: Translocation (14;14)(q11;q32) was associated with acute lymphoblastic leukemia in a child. The B-cell lineage of the leukemic cells led us to perform FISH studies, which showed that the chromosomal breakpoints were telomeric to TCRA/D and IGH loci. These findings show that FISH analyses are necessary when unusual features are associated with a recurrent translocation.
  Cancer Genetics and Cytogenetics 11/2001; 130(1):84-6. · 1.39 Impact Factor
• Article: A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia.

  O A Bernard, M Busson-LeConiat, P Ballerini, M Mauchauffé, V Della Valle, R Monni, F Nguyen Khac, T Mercher, V Penard-Lacronique, P Pasturaud, L Gressin, R Heilig, M T Daniel, M Lessard, R Berger
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  ABSTRACT: FISH identified a cryptic t(5;14)(q35;q32) in T acute lymphoblastic leukemia (ALL), whereas it was not observed in B ALL samples. This translocation is present in five out of 23 (22%) children and adolescents with T ALL tested. RanBP17, a gene coding for a member of the importin beta protein family, and Hox11Like2, an orphan homeobox gene were mapped close to the chromosome 5 breakpoints and CTIP2, which is highly expressed during normal T cell differentiation, was localized in the vicinity of the chromosome 14 breakpoints. The Hox11L2 gene was found to be transcriptionally activated as a result of the translocation, probably under the influence of CTIP2 transcriptional regulation elements. These data establish the t(5;14)(q35;q32) as a major abnormality, and Hox11 family member activation as an important pathway in T ALL leukemogenesis.
  Leukemia 11/2001; 15(10):1495-504. · 9.56 Impact Factor
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  Article: Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia.

  T Mercher, M B Coniat, R Monni, M Mauchauffe, F Nguyen Khac, L Gressin, F Mugneret, T Leblanc, N Dastugue, R Berger, O A Bernard
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  ABSTRACT: The recurrent t(1;22)(p13;q13) translocation is exclusively associated with infant acute megakaryoblastic leukemia. We have identified the two genes involved in this translocation. Both genes possess related sequences in the Drosophila genome. The chromosome 22 gene (megakaryocytic acute leukemia, MAL) product is predicted to be involved in chromatin organization, and the chromosome 1 gene (one twenty-two, OTT) product is related to the Drosophila split-end (spen) family of proteins. Drosophila genetic experiments identified spen as involved in connecting the Raf and Hox pathways. Because almost all of the sequences and all of the identified domains of both OTT and MAL proteins are included in the predicted fusion protein, the OTT-MAL fusion could aberrantly modulate chromatin organization, Hox differentiation pathways, or extracellular signaling.
  Proceedings of the National Academy of Sciences 06/2001; 98(10):5776-9. · 9.68 Impact Factor
• Article: The TEL-Jak2 oncoprotein induces Socs1 expression and altered cytokine response in Ba/F3 cells.

  R Monni, S C Santos, M Mauchauffe, R Berger, J Ghysdael, F Gouilleux, S Gisselbrecht, O Bernard, V Penard-Lacronique
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  ABSTRACT: The leukemia-associated TEL-Jak2 fusion protein possesses a constitutive tyrosine kinase activity and transforming properties in hematopoietic cell lines and animal models. In the murine pro-B Ba/F3 cell line, this fusion constitutively activates the Signal Transducer and Activator of Transcription 5 (Stat5) factors and, as a consequence, induces the sustained expression of various Stat5-target genes including the Cytokine Inducible SH2-containing protein (Cis) gene, which codes for a member of the Suppressor of Cytokine Signaling (Socs) protein family. In TEL-Jak2-transformed Ba/F3 cells, we also observed the upregulation of the Socs1 gene, whose product has been reported to negatively regulate the Jak kinase activity. In transient transfection experiments, Socs1 physically interacts with TEL-Jak2 and interferes with the TEL-Jak2-induced phosphorylation and activation of Stat5 factors, probably through the Socs1-induced proteasome-mediated degradation of the fusion protein. Interestingly, TEL-Jak2-expressing Ba/F3 cells were found to be resistant to the anti-proliferative activities of gamma interferon (IFN-gamma) seemingly as a consequence of Socs1 constitutive expression. These results indicate that the Socs1-dependent cytokine feedback loop, although active, is bypassed by the TEL-Jak2 fusion, but may play a role in the leukemogenic process by altering the cytokine responses of the leukemic cells. Our results also suggest that Socs1 plays a role in shutting down the signaling from the normally activated Jak2 kinase by inducing its proteasome-dependent degradation.
  Oncogene 03/2001; 20(7):849-58. · 6.37 Impact Factor
• Article: CALM-AF10 fusion gene in leukemias: simple and inversion-associated translocation (10;11).

  F Salmon-Nguyen, M Busson, M Daniel, T Leblanc, O A Bernard, R Berger
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  ABSTRACT: A translocation (10;11)(p12;q14) was observed in two children, one with acute eosinophilic leukemia and the other with acute T-cell lymphoblastic leukemia. The presence of CALM-AF10 fusion was ascertained by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Fluorescence in situ hybridization (FISH) analysis showed that AF10 gene splitting was associated with partial inversion of chromosome 11 in the first patient. In addition, FISH analysis also determined the orientation of the CALM gene, 5' telomere to 3' centromere on 11q.
  Cancer Genetics and Cytogenetics 11/2000; 122(2):137-40. · 1.39 Impact Factor
• Article: Location and function of critical genes in leukemogenesis inferred from cytogenetic abnormalities in hematologic malignancies.

  O A Bernard, R Berger
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  ABSTRACT: Dramatic advances in the cytogenetic analysis of chromosomal rearrangements of hematopoietic malignancies have occurred over the past years. These are due to considerable improvement in the techniques of molecular cytogenetics. Various applications of fluorescence in situ hybridization (FISH), used in conjunction with conventional cytogenetics, make the recognition of some abnormalities easier, and the localization of chromosomal breakpoints in structural rearrangements more precise. Under many circumstances, accurate breakpoint localization is the first step toward the identification of genes involved in translocations and inversions. Some of the genes recently discovered may be rearranged with several partner genes. These promiscuous genes are natural experiments that generate mutants which help to identify the function of genes rearranged in hematopoietic malignancies as well as that of their normal counterparts. The diversity of the genes implicated in leukemogenesis makes their functional study a challenge, but, as recently shown by their role in chromatin remodeling, increasing recognition of cross-talk between many of these genes justifies the development of analyses of leukemia-associated chromosome abnormalities and of their functional consequences.
  Seminars in Hematology 11/2000; 37(4):412-9. · 3.99 Impact Factor