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Alexandra Traverse-Glehen,
Emmanuel Bachy,
Lucile Baseggio, Evelyne Callet-Bauchu,
Sophie Gazzo,
Aurélie Verney,
Sandrine Hayette,
Laurent Jallades,
Martine Ffrench,
Gilles Salles,
Bertrand Coiffier,
Pascale Felman,
Francoise Berger
[show abstract]
[hide abstract]
ABSTRACT: To describe 76 cases of splenic marginal zone lymphoma (SMZL), including correlations with clinical and other characteristics.
Patients were predominantly female, with a median age of 62 years. The main clinical presentation was splenomegaly, except for eight cases presenting with evolution of autoimmune disorders or spontaneous splenic rupture. White pulp infiltration was nodular, with a monophasic (42%) or biphasic (53%) pattern, and associated diffuse or nodular infiltration of the red pulp, except for four cases which had atrophic white pulp. Plasmacytic differentiation and the MYD88 L265P mutation were observed in 18% and 5% of the cases, respectively. Histological progression was considered in cases with a significant association of large cells with Ki67 > 30% and macronodular architecture (P = 0.001). Other significant correlations were found between del7q (44%) and del6q (17%) (P = 0.018), IGHV1-2*04 segment usage (35%) (P = 0.001) and unmutated IGHV (39%) (P = 0.019), and between CD5 expression (27%) and higher lymphocytosis (P = 0.002). Patients requiring intensive chemotherapy after splenectomy because of clinical and/or histological progression had significantly shorter overall survival (P = 0.012).
We report the histological spectrum of SMZL, and discuss the differential diagnosis and requirement for molecular and cytogenetic analysis in atypical cases.
Histopathology 05/2013; 62(6):876-93. · 3.08 Impact Factor
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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
[show abstract]
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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
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Violaine Havelange,
Geneviève Ameye,
Ivan Théate, Evelyne Callet-Bauchu,
Francine Mugneret,
Lucienne Michaux,
Nicole Dastugue,
Dominique Penther,
Carole Barin,
Marie-Agnès Collonge-Rame, [......],
Nathalie Nadal,
Eric Lippert,
Jean-Luc Laï,
Christine Cabrol,
Isabelle Tigaud,
Christian Herens,
Anne Hagemeijer,
Martine Raphael,
Jeanne-Marie Libouton,
Hélène A Poirel
[show abstract]
[hide abstract]
ABSTRACT: We previously showed that complex karyotypes (CK) and chromosome 13q abnormalities have an adverse prognostic impact in childhood Burkitt lymphomas/leukemias (BL) and diffuse large B-cell lymphomas (DLBCL). The aim of our study was to identify recurrent alterations associated with MYC rearrangements in aggressive B-cell lymphomas with CK. Multicolor fluorescence in situ hybridization (M-FISH) was performed in 84 patient samples (59 adults and 25 children), including 37 BL (13 lymphomas and 24 acute leukemias), 12 DLBCL, 28 B-cell lymphomas with intermediate features (DLBCL/BL), 4 B-cell precursor acute lymphoblastic leukemias (BCP-ALL), and 3 unclassifiable B-cell lymphomas. New (cytogenetically undetected) abnormalities were identified in 80% of patients. We also refined one-third of the chromosomal aberrations detected by karyotyping. M-FISH proved to be more useful in identifying chromosomal partners involved in unbalanced translocations and in revealing greater complexity of 13q rearrangements. Most of the newly identified or refined recurrent alterations involved 1q, 13q and 3q (gains/losses), 7q and 18q (gains), or 6q (losses), suggesting that these secondary aberrations may play a role in lymphomagenesis. Several patterns of genomic aberrations were identified: 1q gains in BL, trisomies 7 in DLBCL, and 18q-translocations in adult non-BL. BCP-ALL usually displayed an 18q21 rearrangement. BL karyotypes were less complex and aneuploid than those of other MYC-rearranged lymphomas. BCP-ALL and DLBCL/BL were associated with a higher rate of early death than BL and DLBCL. These findings support the categorization of DLBCL/BL as a distinct entity and suggest that BL with CK are indeed different from other aggressive MYC-rearranged lymphomas, which usually show greater genetic complexity. © 2012 Wiley Periodicals, Inc.
Genes Chromosomes and Cancer 09/2012; · 3.31 Impact Factor
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Lucile Baseggio,
Marie-Odile Geay,
Sophie Gazzo,
Françoise Berger,
Alexandra Traverse-Glehen,
Martine Ffrench,
Sandrine Hayette, Evelyne Callet-Bauchu,
Aurélie Verney,
Dominique Morel,
Laurent Jallades,
Jean-Pierre Magaud,
Gilles Salles,
Pascale Felman
[show abstract]
[hide abstract]
ABSTRACT: The translocation t(14;18) and its t(2;18) and t(18,22) variants, which involve the BCL2 genetic hallmark for follicular lymphoma (FL), have been reported in several cases of chronic B-cell lymphoproliferative disease (CLPD) and frequently in chronic lymphocytic leukaemia (CLL). We describe here the clinical, morphological, immunological, cytogenetic and molecular findings from 37 cases of t(14;18)-positive CLPD, identified from our series of non-FL B-cell neoplasms (n=993) that were routinely analysed in peripheral blood by conventional cytogenetics analyses. The FL diagnosis was excluded by morphology and immunology (the samples were CD10 negative in all cases). The BCL2 translocations were observed in 22 CLL cases, including 7 monoclonal B-cell lymphocytosis (MBL) cases re-classified according to the new International Workshop on CLL criteria, six small lymphocytic lymphoma (SLL) cases, 1 splenic marginal zone lymphoma (SMZL) case and eight cases of unclassifiable CLPD with overlapping CLL/MZL features. In the CLL cases, the IGH/BCL2 fusion was remarkably associated with trisomy 12 (13/22) and mutated IGHV status (20/21) and did not affect the outcome. Moreover, most of these CLLs harboured a low mutation load of BCL6 gene and unmutated FAS (CD95) loci, which points to a post-germinal-centre cellular origin.
British Journal of Haematology 06/2012; 158(4):489-98. · 4.94 Impact Factor
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British Journal of Haematology 09/2011; 156(2):279-81. · 4.94 Impact Factor
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Delphine Rolland,
Ali Bouamrani,
Rémi Houlgatte,
Aurélie Barbarat,
Claire Ramus,
Marie Arlotto,
Benoît Ballester,
Françoise Berger,
Pascale Felman, Evelyne Callet-Bauchu,
Lucile Baseggio,
Alexandra Traverse-Glehen,
Sabine Brugière,
Jérôme Garin,
Bertrand Coiffier,
François Berger,
Catherine Thieblemont
[show abstract]
[hide abstract]
ABSTRACT: Mantle cell lymphoma (MCL), small lymphocytic lymphoma (SLL), and marginal zone lymphoma (MZL) are small B-cell non-Hodgkin lymphomas (NHLs) that may be difficult to distinguish. In order to identify specific proteomic biomarkers, differential proteomic analysis of these three NHLs was performed using surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). Whole cell lysates obtained from 18 MCL, 20 SLL, and 20 MZL biopsies were applied on two different ProteinChips (cationic and anionic). Hierarchical clustering and discriminating scores combined with an innovative bio-informatics microdissection strategy allowed us to distinguish specific lymphoma proteomic signatures based on the expression of 37 protein peaks. SELDI-assisted protein purification combined with nano-liquid chromatography (LC) quadrupole-time of flight tandem mass spectrometry (Q-TOF MS/MS) was used to identify proteins overexpressed in both MCL and SLL tumors. Among them two histones, H2B and H4, were identified in MCL tumor biopsies and the signal recognition particle 9 kDa protein, SRP9, in SLL tumor biopsies.
Leukemia & lymphoma 04/2011; 52(4):648-58. · 2.40 Impact Factor
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Florence Nguyen-Khac,
Elise Chapiro,
Claude Lesty,
Aurore Grelier,
Isabelle Luquet,
Isabelle Radford-Weiss,
Christine Lefebvre,
Sandra Fert-Ferrer, Evelyne Callet-Bauchu,
Eric Lippert, [......],
Stéphanie Struski,
Pascaline Talmant,
Laurence Baranger,
Nathalie Gachard,
Carine Gervais,
Benoit Quilichini,
Catherine Settegrana,
Karim Maloum,
Frederic Davi,
Hélène Merle-Béral
[show abstract]
[hide abstract]
ABSTRACT: Chromosomal translocations are usually analyzed as a single entity, and are associated with a poor outcome in chronic lymphocytic leukemia. Translocations involving immunoglobulin genes are recurrent, but uncommon (<5%), and their individual prognosis is not clear. The two most frequent partners are BCL2 (18q21) and BCL3 (19q13).
Herein, 75 cases are reported of chronic lymphocytic leukemia and t(14;18) (BCL2-CLLs). Our series benefits from morphological, immunological and cytogenetical reviews. The IGHV status analyses were performed by referring laboratories. Comparison was made with our previously published series of chronic lymphocytic leukemia patients with t(14;19) (BCL3-CLLs, n=29).
Compared with BCL3-CLLs, lymphocytosis was lower in BCL2-CLLs (p<0.008), and splenomegaly was less frequent (p<0.0001). There were more "typical" morphologies (p<0.005) and Matutes scores >4 (p<0.001) in the BCL2-CLLs group, and less CD38 expression (p<0.04). More variant BCL2-translocations were observed (t(18;22), n=11; 2t(2;18), n=2; p<0.02), and BCL2-translocation was frequently single (p<0.002). Complex karyotypes (p<0.02), trisomy 12 (p<0.03), 6q deletion (p<0.002) and TP53 deletion (p<0.02) were less frequent in BCL2-CLLs, whereas 13q deletion was more frequent (p<0.005). The IGHV gene was frequently mutated in BCL2-CLLs (p<0.0001). Treatment-free survival was longer in BCL2-CLLs (p<0.0001).
BCL2-CLL.S express CD5 and lack expression of CD38, and have a Matutes score ≥4, frequent trisomy 12, no ATM and 6q deletions, and a mutated IGHV status. Compared to BCL3-CLLs, BCL2-CLLs are much less aggressive; indicating that identifying individual translocations and cytogenetic partners would allow improved patient stratification.
American journal of blood research. 01/2011; 1(1):13-21.
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Inga Nagel,
Monika Szczepanowski,
José I Martín-Subero,
Lana Harder,
Takashi Akasaka,
Ole Ammerpohl, Evelyne Callet-Bauchu,
Randy D Gascoyne,
Stefan Gesk,
Doug Horsman,
Wolfram Klapper,
Aneela Majid,
José A Martinez-Climent,
Stephan Stilgenbauer,
Holger Tönnies,
Martin J S Dyer,
Reiner Siebert
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[hide abstract]
ABSTRACT: Sequence variants at the TERT-CLPTM1L locus in chromosome 5p have been recently associated with disposition for various cancers. Here we show that this locus including the gene encoding the telomerase reverse-transcriptase TERT at 5p13.33 is rarely but recurrently targeted by somatic chromosomal translocations to IGH and non-IG loci in B-cell neoplasms, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, mantle cell lymphoma and splenic marginal zone lymphoma. In addition, cases with genomic amplification of TERT locus were identified. Tumors bearing chromosomal aberrations involving TERT showed higher TERT transcriptional expression and increased telomerase activity. These data suggest that deregulation of TERT gene by chromosomal abnormalities leading to increased telomerase activity might contribute to B-cell lymphomagenesis.
Blood 05/2010; 116(8):1317-20. · 9.90 Impact Factor
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Christiane Pott,
Eva Hoster,
Marie-Helene Delfau-Larue,
Kheira Beldjord,
Sebastian Böttcher,
Vahid Asnafi,
Anne Plonquet,
Reiner Siebert, Evelyne Callet-Bauchu,
Niels Andersen, [......],
Marek Trneny,
Jan Walewski,
Peter Dreger,
Michael Unterhalt,
Wolfgang Hiddemann,
Michael Kneba,
Hanneke C Kluin-Nelemans,
Olivier Hermine,
Elizabeth Macintyre,
Martin Dreyling
[show abstract]
[hide abstract]
ABSTRACT: The prognostic impact of minimal residual disease (MRD) was analyzed in 259 patients with mantle cell lymphoma (MCL) treated within 2 randomized trials of the European MCL Network (MCL Younger and MCL Elderly trial). After rituximab-based induction treatment, 106 of 190 evaluable patients (56%) achieved a molecular remission (MR) based on blood and/or bone marrow (BM) analysis. MR resulted in a significantly improved response duration (RD; 87% vs 61% patients in remission at 2 years, P = .004) and emerged to be an independent prognostic factor for RD (hazard ratio = 0.4, 95% confidence interval, 0.1-0.9, P = .028). MR was highly predictive for prolonged RD independent of clinical response (complete response [CR], complete response unconfirmed [CRu], partial response [PR]; RD at 2 years: 94% in BM MRD-negative CR/CRu and 100% in BM MRD-negative PR, compared with 71% in BM MRD-positive CR/CRu and 51% in BM MRD-positive PR, P = .002). Sustained MR during the postinduction period was predictive for outcome in MCL Younger after autologous stem cell transplantation (ASCT; RD at 2 years 100% vs 65%, P = .001) and during maintenance in MCL Elderly (RD at 2 years: 76% vs 36%, P = .015). ASCT increased the proportion of patients in MR from 55% before high-dose therapy to 72% thereafter. Sequential MRD monitoring is a powerful predictor for treatment outcome in MCL. These trials are registered at www.clinicaltrials.gov as #NCT00209222 and #NCT00209209.
Blood 04/2010; 115(16):3215-23. · 9.90 Impact Factor
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British Journal of Haematology 03/2010; 150(1):113-6. · 4.94 Impact Factor
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[show abstract]
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ABSTRACT: PURPOSE Patients with diffuse large B-cell lymphoma (DLBCL) usually relapse early following diagnosis but some relapses happen at 5 years or later. Few data exist regarding clinical characteristics and outcome of these patients. PATIENTS AND METHODS We performed a retrospective analysis of all patients from two centers in Lyon, France, between 1985 and 2003 who had a biopsy-proven relapse 5 years or later following diagnosis of DLBCL. All available biopsies were reviewed and immunohistochemistry was completed. Results Among 1,492 patients with DLBCL, 54 were eligible. At diagnosis, 63% of patients had stage I-II, 82% had low/low-intermediate International Prognostic Index (IPI) score, 65% had extranodal involvement, 24% had an indolent component associated with DLBCL, 57% had germinal center phenotype, and 43% had non-germinal center phenotype. Median time from diagnosis to relapse was 7.4 years (range, 5 to 20.5 years). At time of relapse, 83% had DLBCL histology, and 17% had indolent histology. Having an indolent component at diagnosis was associated with indolent histology at relapse (P = .028). Five-year event free-survival (EFS) was 17% for patients with DLBCL relapse and 61% for patients with indolent relapse (P = .027). Five-year overall survival was 27% for patients with DLBCL and 75% for patients with indolent relapse (P = .029). For DLBCL relapse, 3-year EFS was 56% versus 18% with autologous stem-cell transplantation or not, respectively (P = .0661). CONCLUSION Patients with DLBCL who had a late relapse usually had localized stage, favorable IPI score, and extranodal involvement at diagnosis. The outcome of patients with DLBCL at time of relapse remains poor, and aggressive treatment such as autologous stem-cell transplantation should be pursued whenever possible. Biopsy at relapse is essential because some patients relapse with indolent histology.
Journal of Clinical Oncology 03/2010; 28(12):2094-100. · 18.37 Impact Factor
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Lucile Baseggio,
Alexandra Traverse-Glehen,
Florence Petinataud, Evelyne Callet-Bauchu,
Françoise Berger,
Martine Ffrench,
Chantal Marie Couris,
Catherine Thieblemont,
Dominique Morel,
Bertrand Coiffier,
Gilles Salles,
Pascale Felman
[show abstract]
[hide abstract]
ABSTRACT: Classically, splenic marginal zone B-cell lymphoma is characterized by the absence of CD5 expression. Cases of apparent splenic marginal zone B-cell lymphoma showing CD5 expression, as diagnosed by blood studies, have been described; however, in the absence of histological evidence, the correct diagnosis of these cases is controversial because of possible confusion with other CD5-positive small B-cell neoplasms.
We report a series of 24 CD5-positive, t(11;14)-negative cases of splenic marginal zone B-cell lymphoma diagnosed by flow cytometry studies of blood and histologically proven on spleen sections. Clinical data as well as morphological, immunological, cytogenetic and molecular characteristics were assessed to evaluate the similarities and differences of these cases with those of classical CD5-negative splenic marginal zone B-cell lymphoma.
The CD5 expression detected in blood by flow cytometry was confirmed in most cases by immunohistochemistry on spleen sections. In general, cases of CD5-positive and CD5-negative splenic marginal zone B-cell lymphoma did not appear different and, in particular, they showed similar karyotypic changes such as 7q deletion, trisomy 3, trisomy 18 and biased IGHV usage (i.e. VH1-2). The main differences were a higher lymphocyte count at diagnosis (8.15x10(9)/L versus 3.90x10(9)/L; P=0.005) and more frequent diffuse bone marrow infiltration (34% versus 8%; P=0.03) in the CD5-positive group. A tendency to a more mutated IGHV status in the CD5 positive cases was observed (80% versus 54.5%; (P=0.11). No significant differences in outcome were found in relation to CD5 expression.
This study confirms the existence of cases of CD5-positive splenic marginal zone B-cell lymphoma and shows that these cases are closely related to classical splenic marginal zone lymphoma. Whether or not CD5-positive splenic marginal zone B-cell lymphoma constitutes a true subset obviously requires the study of more cases.
Haematologica 12/2009; 95(4):604-12. · 6.42 Impact Factor
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Eva Maria Murga Penas, Evelyne Callet-Bauchu,
Hongtao Ye,
Sophie Gazzo,
Françoise Berger,
Georgia Schilling,
Nadine Albert-Konetzny,
Eik Vettorazzi,
Gilles Salles,
Iwona Wlodarska,
Ming-Qing Du,
Carsten Bokemeyer,
Judith Dierlamm
[show abstract]
[hide abstract]
ABSTRACT: The t(14;18)(q32;q21) involving the immunoglobulin heavy chain locus (IGH) and the MALT1 gene is a recurrent abnormality in mucosa-associated lymphoid tissue (MALT) lymphomas. However, the nucleotide sequence of only one t(14;18)-positive MALT lymphoma has been reported so far. We here report the molecular characterization of the IGH-MALT1 fusion products in 5 new cases of t(14;18)-positive MALT lymphomas. Similar to the IGH-associated translocations in follicular and mantle cell lymphomas, the IGH-MALT1 junctions in MALT lymphoma showed all features of a recombination signal sequence-guided V(D)J-mediated translocation at the IGH locus. Furthermore, analogous to follicular and mantle cell lymphoma, templated nucleotides (T-nucleotides) were identified at the t(14;18)/IGH-MALT1 breakpoint junctions. On chromosome 18, we identified a novel major breakpoint region in MALT1 upstream of its coding region. Moreover, the presence of duplications of MALT1 nucleotides in one case suggests an underlying staggered DNA-break process not consistent with V(D)J-mediated recombination. The molecular characteristics of the t(14;18)/IGH-MALT1 resemble those found in the t(14;18)/IGH-BCL2 in follicular lymphoma and t(11;14)/CCND1-IGH in mantle cell lymphoma, suggesting that these translocations could be generated by common pathomechanisms involving illegitimate V(D)J-mediated recombination on IGH as well as new synthesis of T-nucleotides and nonhomologous end joining (NHEJ) or alternative NHEJ repair pathways on the IGH-translocation partner.
Blood 11/2009; 115(11):2214-9. · 9.90 Impact Factor
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Alexandre Ottaviani,
Caroline Schluth-Bolard,
Sylvie Rival-Gervier,
Amina Boussouar,
Delphine Rondier,
Andrea M Foerster,
Julia Morere,
Serge Bauwens,
Sophie Gazzo, Evelyne Callet-Bauchu,
Eric Gilson,
Frédérique Magdinier
[show abstract]
[hide abstract]
ABSTRACT: The localization of genes within the nuclear space is of paramount importance for proper genome functions. However, very little is known on the cis-acting elements determining subnuclear positioning of chromosome segments. We show here that the D4Z4 human subtelomeric repeat localizes a telomere at the nuclear periphery. This perinuclear activity lies within an 80 bp sequence included within a region known to interact with CTCF and A-type Lamins. We further show that a reduced level of either CTCF or A-type Lamins suppresses the perinuclear activities of D4Z4 and that an array of multimerized D4Z4 sequence, which has lost its ability to bind CTCF and A-type Lamins, is not localized at the periphery. Overall, these findings reveal the existence of an 80 bp D4Z4 sequence that is sufficient to position an adjacent telomere to the nuclear periphery in a CTCF and A-type lamins-dependent manner. Strikingly, this sequence includes a 30 bp GA-rich motif, which binds CTCF and is present at several locations in the human genome.
The EMBO Journal 08/2009; 28(16):2428-36. · 9.20 Impact Factor
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Elise Chapiro,
Nathalie Leporrier,
Isabelle Radford-Weiss,
Christian Bastard,
Hossein Mossafa,
Dominique Leroux,
Isabelle Tigaud,
Marc De Braekeleer,
Christine Terré,
Françoise Brizard, [......],
Lauren Veronese,
Sandra Fert-Ferrer,
Sylvie Taviaux,
Claude Lesty,
Frédéric Davi,
Hélène Merle-Béral,
Olivier A Bernard,
Laurent Sutton,
Sophie D Raynaud,
Florence Nguyen-Khac
[show abstract]
[hide abstract]
ABSTRACT: Using array-based CGH, we identified 2p gain in 22/78 (28%) untreated Binet stages B/C CLL, which was the second most frequent copy number change after 13q deletion. It never occurred as a sole abnormality and was associated with other changes (6q deletion; 1p gain). The region of 2p gain frequently included two oncogenes, REL and MYCN. All patients with gain of REL were unmutated for IGHV (p=0.03). Gain of MYCN was associated with increased mRNA expression (p=0.005), suggesting a pathogenic role for MYCN. Gain of 2p appears to be a marker of progression and may contribute to the poor prognosis.
Leukemia research 05/2009; 34(1):63-8. · 2.36 Impact Factor
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Catherine Thieblemont,
Delphine Rolland,
Lucile Baseggio,
Pascale Felman,
Sophie Gazzo, Evelyne Callet-Bauchu,
Alexandra Traverse-Glehen,
Rémi Houlgatte,
Kai Fu,
Dennis Weisenburger,
Daphne De Jong,
Elaine S Jaffe,
Andreas Rosenwald,
German Ott,
Bertrand Coiffier,
Françoise Berger
Leukemia & lymphoma 08/2008; 49(7):1403-6. · 2.40 Impact Factor
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Delphine Poncet,
Aurélie Belleville,
Claire t'kint de Roodenbeke,
Aude Roborel de Climens,
Elsa Ben Simon,
Hélène Merle-Beral, Evelyne Callet-Bauchu,
Gilles Salles,
Laure Sabatier,
Jozo Delic,
Eric Gilson
[show abstract]
[hide abstract]
ABSTRACT: In this study, we explored the telomeric changes that occur in B-chronic lymphocytic leukemia (B-CLL), in which telomere length has recently been demonstrated to be a powerful prognostic marker. We carried out a transcriptomic analysis of telomerase components (hTERT and DYSKERIN), shelterin proteins (TRF1, TRF2, hRAP1, TIN2, POT1, and TPP1), and a set of multifunctional proteins involved in telomere maintenance (hEST1A, MRE11, RAD50, Ku80, and RPA1) in peripheral B cells from 42 B-CLL patients and 20 healthy donors. We found that, in B-CLL cells, the expressions of hTERT, DYSKERIN, TRF1, hRAP1, POT1, hEST1A, MRE11, RAD50, and KU80 were more than 2-fold reduced (P < .001), contrasting with the higher expression of TPP1 and RPA1 (P < .001). This differential expression pattern suggests that both telomerase down-regulation and changes in telomeric proteins composition are involved in the pathogenesis of B-CLL.
Blood 03/2008; 111(4):2388-91. · 9.90 Impact Factor
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Alexandra Traverse-Glehen,
Lucile Baseggio, Evelyne Callet- Bauchu,
Dominique Morel,
Sophie Gazzo,
Martine Ffrench,
Aurélie Verney,
Delphine Rolland,
Catherine Thieblemont,
Jean-Pierre Magaud,
Gilles Salles,
Bertrand Coiffier,
Françoise Berger,
Pascale Felman
[show abstract]
[hide abstract]
ABSTRACT: The presence of circulating villous lymphocytes (VLs) in lymphoma patients usually points to splenic marginal zone B-cell lymphoma (SMZL), even if the VLs can be found occasionally in other small B-cell lymphomas. However, those cells are variably described, and detailed cytologic characterization is often lacking. We identified lymphoma cases with numerous basophilic VLs among the large group of splenic lymphoma with VLs, and for further delineation, 37 cases with this particular cytology were analyzed. Patients, predominantly older men, presented with moderate lymphocytosis and splenomegaly without pancytopenia. The monoclonal B cells expressed IgM + D, IgM + G, IgM or IgG, as well as CD76 and CD11c, frequently CD103, and rarely CD123. Spleen sections were peculiar, with atrophic white pulp and a monomorphic diffuse lymphoma infiltration in a congested red pulp. Bone marrow infiltration was interstitial and intrasinusoidal without extensive fibrosis. Cytogenetic analysis showed a frequent absence of clonal aberrations (68%). Most cases (79%) were IgH mutated, with an overrepresentation of V(H)3 and V(H)4 gene families. These results, as well as the clinical evolution, show that those lymphoma cases represent a homogeneous group distinct from SMZL and reminiscent of hairy cell leukemia variant, perhaps corresponding to a separate lymphoma entity.
Blood 03/2008; 111(4):2253-60. · 9.90 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: This report deals with a case of Sézary syndrome, a rare peripheral T-cell lymphoproliferative disorder, in which cytogenetic analysis performed during the disease transformation revealed the presence of a t(9;22) (q34;q11.2) translocation. Molecular analyses identified a new transcript, an e8a4 BCR-ABL fusion mRNA which could be responsible for the disease transformation.
Haematologica 10/2007; 92(9):1277-8. · 6.42 Impact Factor
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Florence Lachenal,
Francoise Berger,
Hervé Ghesquières,
Pierre Biron,
Arnaud Hot, Evelyne Callet-Bauchu,
Catherine Chassagne,
Bertrand Coiffier,
Isabelle Durieu,
Hugues Rousset,
Gilles Salles
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ABSTRACT: We retrospectively analyzed 77 patients with pathologically diagnosed angioimmunoblastic T-cell lymphoma from a single city. There were 43 men and 34 women; the median age was 64.5 years (range, 30-91 yr). Average time between first symptoms of the disease and diagnosis was 3.6 months. At diagnosis, peripheral nodes were present in all but 1 patient, and were generalized in 90% of cases. Constitutional symptoms were reported in 77% of cases and spleen enlargement in 51%. A cutaneous eruption--morbilliform, urticarial, or more polymorphic--was present in 45% of patients; in one-third of them, the eruption occurred after drug administration. Other clinical manifestations included pleuritis (22%); arthralgia or arthritis (17%); ear, nose, and throat involvement (14%); central or peripheral neurologic manifestations (10%); and ascites (5%). Most patients presented with advanced disease at diagnosis (bone marrow involvement in 60% of cases). The main laboratory abnormalities were elevated lactate dehydrogenase levels (71%), inflammatory syndrome (67%), hypergammaglobulinemia (50%), anemia (51%), and lymphopenia (52%). Auto- or disimmune manifestations were reported in one-third of patients: autoimmune hemolytic anemia was present at diagnosis in 19% of patients and thrombocytopenic purpura in 7%. Documented vasculitis was described in 12% of cases. Clonality was analyzed in lymph nodes in 47 patients: T-cell and B-cell clones were found in 45 (96%) and 20 (45%) patients, respectively. Chromosomal abnormalities were identified in 62% of cases: trisomies 3, 5, 18, 19, additional X chromosome, and deletion of chromosome 7 were the most common abnormalities. The current study underlines the diversity of presenting manifestations of angioimmunoblastic T-cell lymphoma.
Medicine 10/2007; 86(5):282-92. · 4.35 Impact Factor
