H Poirel

Publications (18)150.77 Total impact

• 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: 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: Characterization of a novel ETS gene, TELB, encoding a protein structurally and functionally related to TEL.

  H Poirel, R G Lopez, V Lacronique, V Della Valle, M Mauchauffé, R Berger, J Ghysdael, O A Bernard
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  ABSTRACT: The TEL/ETV6 gene is located at 12p13 and is frequently involved in chromosomal translocations in human malignancies usually resulting in the expression of fusion proteins between the amino terminal part of TEL, and either unrelated transcription factors or protein tyrosine kinases. We report here a novel gene named TELB which is located on human chromosomal band 6p21 and encodes a protein highly related to TEL. TELB is widely expressed in different tissues and, similarly to TEL encodes a sequence-specific transcriptional repressor.
  Oncogene 10/2000; 19(41):4802-6. · 6.37 Impact Factor
• Article: The leukaemic oncoproteins Bcr-Abl and Tel-Abl (ETV6/Abl) have altered substrate preferences and activate similar intracellular signalling pathways.

  J Voss, G Posern, J R Hannemann, L M Wiedemann, A G Turhan, H Poirel, O A Bernard, K Adermann, C Kardinal, S M Feller
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  ABSTRACT: Inappropriate activation of Abl family kinases plays a crucial role in different human leukaemias. In addition to the well known oncoproteins p190Bcr-Abl and p210Bcr-Abl, Tel-Abl, a novel fusion protein resulting from a different chromosomal translocation, has recently been described. In this study, the kinase specificities of the Bcr-Abl and Tel-Abl proteins were compared to the physiological Abl family kinases c-Abl and Arg (abl related gene). Using short peptides which correspond to the target epitopes in known substrate proteins of Abl family kinases, we found a higher catalytic promiscuity of Bcr-Abl and Tel-Abl. Similar to Bcr-Abl, Tel-Abl was found in complexes with the adapter protein CRKL. In addition, c-Crk II and CRKL are tyrosine phosphorylated and complexed with numerous other tyrosine phosphorylated proteins in Tel-Abl expressing Ba/F3 cells. GTPase analysis with a Ras-GTP-specific precipitation assay showed constitutive elevation of GTP-loaded Ras in cells expressing the leukaemic Abl proteins. The mitogenic MAPK/Erk kinases as well as Akt/PKB, a kinase implicated to negatively regulate apoptosis, were also constitutively activated by both Bcr-Abl and Tel-Abl. The results indicate that the leukaemic Abl-fusion proteins have catalytic specificities different from the normal kinases c-Abl and Arg and that Tel-Abl is capable to activate at least some pathways which are also upregulated by Bcr-Abl.
  Oncogene 04/2000; 19(13):1684-90. · 6.37 Impact Factor
• Article: Molecular analysis of chromosomal breakpoints in three examples of chromosomal translocation involving the TEL gene.

  S Romana, H Poirel, V Della Valle, M Mauchauffé, M Busson-Le Coniat, R Berger, O A Bernard
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  ABSTRACT: The TEL gene is involved in several chromosomal abnormalities of human hematopoietic malignancies. The chromosome 12 breakpoints frequently lie within the fifth intron of the gene, particularly in the most frequent translocation involving TEL, the t(12;21)(p13;q22). In order to search for a peculiar mechanism involved in the genesis of these translocations, we have established the sequence of two t(12;21) and a t(9;12)(q24;p13) breakpoints. Our data do not reveal the involvement of VDJ recombinase activity or Alu sequences but favor the occurrence of staggered breaks and DNA repair activity in the genesis of these translocations.
  Leukemia 12/1999; 13(11):1754-9. · 9.56 Impact Factor
• Article: Loss of the TEL/ETV6 gene by a second translocation in ALL patients with t(12;21).

  M B Coniat, H Poirel, T Leblanc, O A Bernard, R Berger
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  ABSTRACT: Inactivation of the non translocated TEL/ETV6 gene is commonly associated with translocation (12;21) of acute lymphoblastic leukemia (ALL). Translocations involving the short arm of chromosome 12 were analysed in two children with t(12;21) ALL. Fluorescence in situ hybridation studies showed that these associated translocations resulted in loss of TEL/ETV6. While hybridization with a YAC probe covering TEL/ETV6 was positive in one patient, analysis with cosmid probes covering the gene demonstrated that the gene was in fact deleted. It is concluded that deletions involving TEL/ETV6 can remain undetected by FISH using only YAC probes.
  Leukemia Research 11/1999; 23(10):895-9. · 2.92 Impact Factor
• Article: Analysis of TEL proteins in human leukemias.

  H Poirel, V Lacronique, M Mauchauffé, M Le Coniat, E Raffoux, M T Daniel, P Erickson, H Drabkin, R A MacLeod, H G Drexler, J Ghysdael, R Berger, O A Bernard
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  ABSTRACT: Chromosomal translocations involving the human 12p13 band frequently affect the TEL gene, usually resulting in gene fusion between TEL and genes encoding proteins of various types. The most frequent 12p13 translocation is the t(12;21)(p13;q22), which recombines TEL with the AML1 gene on chromosome 21 and is frequently associated with deletion of the untranslocated TEL allele. Using antisera against different parts of TEL and against the AML1 proteins, we undertook Western blot and immunofluorescence analyses of leukemic samples with and without 12p13 abnormalities. In t(12;21) samples, TEL-AML1 was detected as several protein species in the nuclei, whereas the AML1-TEL protein, was inconsistently expressed. AML1 was found to be expressed but no normal TEL proteins were detected. A survey of the TEL proteins in a panel of human leukemic samples without t(12;21) revealed a variation in the ratio of TEL protein isoforms. We also analysed a leukemic cell line bearing a t(12;22)(p13;q11) that was found to affect the 5' untranslated (UT) region of TEL and to be associated with inactivation of the untranslocated TEL allele. No MN1-TEL fusion could be detected upon RT-PCR analysis, in contrast to the previously investigated t(12;22). Strikingly, extremely low levels of apparently normal TEL proteins, expressed from the translocated allele, were detected by Western blot analysis. These results suggest that the level of TEL expression can be important for leukemogenesis.
  Oncogene 07/1998; 16(22):2895-903. · 6.37 Impact Factor
• Article: A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia.

  V Lacronique, A Boureux, V D Valle, H Poirel, C T Quang, M Mauchauffé, C Berthou, M Lessard, R Berger, J Ghysdael, O A Bernard
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  ABSTRACT: The Janus family of tyrosine kinases (JAK) plays an essential role in development and in coupling cytokine receptors to downstream intracellular signaling events. A t(9;12)(p24;p13) chromosomal translocation in a T cell childhood acute lymphoblastic leukemia patient was characterized and shown to fuse the 3' portion of JAK2 to the 5' region of TEL, a gene encoding a member of the ETS transcription factor family. The TEL-JAK2 fusion protein includes the catalytic domain of JAK2 and the TEL-specific oligomerization domain. TEL-induced oligomerization of TEL-JAK2 resulted in the constitutive activation of its tyrosine kinase activity and conferred cytokine-independent proliferation to the interleukin-3-dependent Ba/F3 hematopoietic cell line.
  Science 12/1997; 278(5341):1309-12. · 31.20 Impact Factor
• Source

  Available from: hematologylibrary.org

  Article: Prognosis value of residual disease monitoring by polymerase chain reaction in patients with CBF beta/MYH11-positive acute myeloblastic leukemia.

  R Costello, D Sainty, D Blaise, J A Gastaut, J Gabert, H Poirel, A Buzyn-Veil, E Macintyre
  Blood 04/1997; 89(6):2222-3. · 9.90 Impact Factor
• Article: The TEL gene products: nuclear phosphoproteins with DNA binding properties.

  H Poirel, C Oury, C Carron, E Duprez, Y Laabi, A Tsapis, S P Romana, M Mauchauffe, M Le Coniat, R Berger, J Ghysdael, O A Bernard
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  ABSTRACT: The human TEL gene is involved in several 12p13 chromosomal abnormalities present in various human hematological malignancies, the most frequent being the t(12;21)(p13;q22), specific for childhood acute lymphoblastic leukemia. The predicted product of TEL harbours an amino acid region similar to the ETS DNA binding domain. We now report the isolation of the murine TEL cDNA and the characterization of the human TEL proteins. Human and murine TEL proteins are particularly homologous within their aminoterminal regions and their ETS domains. TEL proteins are nuclear and display specific DNA binding activity toward classical ETS binding sites. In addition, we show that TEL mRNAs initiate translation at either of the two first inframe ATGs (codon 1 and 43) to encode 50 kDa and 57 kDa TEL proteins. In vivo, each of these primary translational products is modified by multiple phosphorylation events.
  Oncogene 02/1997; 14(3):349-57. · 6.37 Impact Factor
• Article: Molecular cytogenetics of t(12;21) (p13;q22).

  O A Bernard, S P Romana, H Poirel, R Berger
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  ABSTRACT: The translocation t(12;21)(p13;q22) is a frequent nonrandom rearrangement of B-cell lineage childhood acute lymphoblastic leukemia (ALL) which fuses the TEL and AML1 genes, normally localized to 12p13 and 21q22, respectively. The crucial chimeric gene, TEL-AML1, is transcribed from the der(21) and encodes the 336 NH2 aminoacics of TEL fused to the majority of the AML1 protein. The t(12;21) is very often associated with loss of the normal, untranslocated TEL allele. These various aspects are presented here.
  Leukemia and Lymphoma 12/1996; 23(5-6):459-65. · 2.58 Impact Factor
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  Available from: hematologylibrary.org

  Article: Incidence and characterization of MLL gene (11q23) rearrangements in acute myeloid leukemia M1 and M5.

  H Poirel, K Rack, E Delabesse, I Radford-Weiss, X Troussard, C Debert, D Leboeuf, C Bastard, F Picard, A Veil-Buzyn, G Flandrin, O Bernard, E Macintyre
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  ABSTRACT: To determine the incidence of MLL rearrangement in acute myeloid leukemia (AML) French-American-British (FAB) type M1 and to evaluate optimal screening strategies for the characterization of such abnormalities, we analyzed specimens from 41 patients with AML by Southern blotting with two MLL genomic probes and compared the capacities of reverse transcription-polymerase chain reaction (RT-PCR) and fluorescent in situ hybridization (FISH) to identify the types of rearrangement found in AML M1 with those observed in AML M5. MLL rearrangement was found in 6 of 29 (20%) AML M1 and 6 of 10 AML M5 cases. RT-PCR characterization of 11 cases showed four MLL self-fusions, four MLL-AF6, two MLL-AF9, including a novel AF9 breakpoint, and one uncharacterized t(11:19). Only 5 of 10 MLL-rearranged cases tested demonstrated karyotypic 11q23 abnormalities. FISH analysis of nine cases with an MLL-specific yeast artificial chromosome (YAC) confirmed the cytogenetic abnormalities in two cases, clarified them in one, and did not detect six cases, including three MLL self-fusions, one case with a probable MLL-rearranged subclone not represented karyotypically, and twoMLL-AF6. A whole chromosome 11 paint detected one of these MLL-AF6, and an AF6 cosmid demonstrated that the other was probably due to insertion of a submicroscopic portion of chromosome 6, including part of AF6, into an apparently normal chromosome 11. We conclude that MLL rearrangements are common in adult AML M1, that MLL self-fusion and MLL-AF6 are the most frequent types of abnormalities, and that RT-PCR is preferable to 11q23 FISH analysis for their characterization.
  Blood 04/1996; 87(6):2496-505. · 9.90 Impact Factor
• Article: Sustained complete cytologic and molecular remission induced by donor leucocyte infusions alone in an acute myeloblastic leukaemia in relapse after bone marrow transplantation.

  A Buzyn-Veil, C Belanger, F Audat, O Hermine, C Bodemer, V Ribrag, I Radford, H Poirel, C Chane, F Valensi, E Macintyre, B Varet
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  ABSTRACT: Therapeutic options for treatment of recurrence of leukaemia after allogeneic bone marrow transplantation (BMT) are limited. A beneficial effect of donor lymphocyte infusions (DLI) has not previously been described in acute myeloid leukaemia (AML) relapse. We report a case of AML with t(8;21), relapsing 3 months after BMT, who received DLI without adjuvant chemotherapy or growth factors. The patient developed acute GVHD and achieved a rapid complete remission of his AML by both cytologic and molecular criteria of at least 14 months duration, thereby showing that DLI for AML in relapse after BMT is an alternative therapeutic option.
  British Journal of Haematology 03/1996; 92(2):423-5. · 4.94 Impact Factor
• Article: Deletion of the short arm of chromosome 12 is a secondary event in acute lymphoblastic leukemia with t(12;21).

  S P Romana, M Le Coniat, H Poirel, P Marynen, O Bernard, R Berger
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  ABSTRACT: Translocation t(12;21) has been described as a nonrandom event in acute lymphoblastic leukemia (ALL) in patients with deletion of the short arm of chromosome 12, using fluorescence in situ hybridization techniques. Extensive FISH experiments were performed in order to re-examine the short arm of chromosome 12 in three children with ALL, previously shown to have t(12;21). It was shown that the t(12;21) is undetectable by routine R-banding technique and that the translocated 12 looks like a cytogenetically normal chromosome 12 in the three patients. Partial 12p deletion involving the TEL locus was shown to be interstitial in one patient with 12p- by using cosmid and YAC probes. In the second patient, the 12p- chromosome was secondary to the translocation since it was observed in about one half of the metaphases analyzed with FISH. In the third patient, the region of TEL usually rearranged in the t(12;21) displayed a germline pattern by Southern blotting, at diagnosis and in relapse. A few metaphases showed associated 12p- by standard cytogenetics, only in relapse. Thus we conclude that the TEL allele not involved in t(12;21) is inconstantly lost in patients with this subtype of ALL and occurs on the 12p- chromosome. These data question the status of tumor suppressor gene hypothesized for TEL.
  Leukemia 02/1996; 10(1):167-70. · 9.56 Impact Factor
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  Available from: hematologylibrary.org

  Article: High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia.

  S P Romana, H Poirel, M Leconiat, M A Flexor, M Mauchauffé, P Jonveaux, E A Macintyre, R Berger, O A Bernard
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  ABSTRACT: The recurrent t(12;21)(p12;q22) translocation fuses two genes, TEL and AML1, that have previously been shown to be independently involved in myeloid malignant proliferations. A search for rearrangement of the TEL locus in the region known to be involved in t(12;21) was performed by Southern blotting in a panel of hematopoietic malignancies. The presence of a t(12;21) was confirmed by fluorescence in situ hybridization (FISH) and/or reverse transcriptase (RT)-polymerase chain reaction (PCR). We report that fusion of TEL to AML1 is specifically observed in at least 16% of the childhood B-lineage acute lymphoblastic leukemia (ALL) investigated, none of which had been previously identified as harboring t(12;21).
  Blood 01/1996; 86(11):4263-9. · 9.90 Impact Factor
• Article: A comparative analysis of fall in haemoglobin following abortions conducted by mifepristone (600 mg) and vacuum aspiration.

  P Thonneau, H Poirel, B Fougeyrollas, B Maria, L Meyer, A Goepp, S Hercberg, A Spira
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  ABSTRACT: We compared post-abortion metrorrhagia in 185 women who used the mifepristone (600 mg) plus sulprostone (250 micrograms) drug combination and in 196 women who underwent vacuum aspiration. The patients were monitored for a 2 week period, with haemoglobin being measured on the day of the abortion and 2 weeks later. The women who had used the drug combination experienced a mean fall of 0.7 g/dl in haemoglobin (36% lost > 1 g/dl and 8% > 2 g/dl); haemoglobin concentrations remained stable in women who had had vacuum aspiration.
  Human Reproduction 07/1995; 10(6):1512-5. · 4.47 Impact Factor
• Article: Trisomy 14: a recurring cytogenetic abnormality associated with myeloid disorders.

  H Poirel, P Jonveaux, M T Daniel, R Berger
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  ABSTRACT: Trisomy 14 as single karyotype aberration was detected in three patients, two with acute myeloblastic leukemia, AML-M2 type, and one with aplastic anemia. These new observations and the 28 previously reported cases confirm that trisomy 14 is a primary non random change, mostly confined to myeloid disorders.
  Leukemia and Lymphoma 06/1995; 17(5-6):455-7. · 2.58 Impact Factor
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  Available from: hematologylibrary.org

  Article: Detection of the chromosome 16 CBF beta-MYH11 fusion transcript in myelomonocytic leukemias.

  H Poirel, I Radford-Weiss, K Rack, X Troussard, A Veil, F Valensi, F Picard, M Guesnu, D Leboeuf, J Melle
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  ABSTRACT: Karyotypic detection of chromosomal 16 abnormalities classically associated with AML M4Eo can be difficult. Characterization of the two genes involved in the inv(16)(p13q22), CBF beta and MYH11, has allowed the detection of fusion transcripts by reverse-transcriptase polymerase chain reaction (RT-PCR). We have analyzed CBF beta-MYH11 fusion transcripts by RT-PCR in myelomonocytic leukemias, with or without eosinophilia, to determine whether their presence correlates with morphology. Fifty-three cases (11 AML M4Eo; 1 AML M4 with atypical abnormal eosinophils (AML M4 "Eo"); 29 AML M4; 8 AML M5; 3 CMML; and 1 AML M2 with eosinophilia) were analyzed. All 11 typical AML M4Eo were CBF beta-MYH11 positive. The single case of AML M4 with distinctive eosinophil abnormalities was negative by karyotype, RT-PCR and fluorescent in situ hybridization (FISH). Three of 29 (10%) AML M4 without abnormal eosinophils were CBF beta-MYH11 positive, 1 of which did not show any apparent chromosome 16 abnormalities by classical metaphase analysis (2 not tested). Both cases tested also showed MYH11 genomic rearrangement. None of the other leukemias were RT-PCR positive. Follow-up of three patient showed residual positivity in apparent complete remission. These data show that CBF beta-MYH11 fusion transcripts occur not only in the vast majority of typical AML M4Eo, but also in approximately 10% of AML M4 without eosinophilic abnormalities, a much higher incidence than the sporadic reports of chromosome 16 abnormalities in AML M4 would suggest. Taken together with the detection of CBF beta-MYH11 transcripts in the absence of apparent chromosome 16 abnormalities by classical banding techniques, these data show that additional screening by either RT-PCR or FISH should be performed in all AML M4, regardless of morphologic features, to allow accurate evaluation of the prognostic importance of this fusion transcript.
  Blood 04/1995; 85(5):1313-22. · 9.90 Impact Factor