Literature DB >> 22432063

Specific chromosomal IG translocations have different prognoses in chronic lymphocytic leukemia.

Florence Nguyen-Khac, Elise Chapiro, Claude Lesty, Aurore Grelier, Isabelle Luquet, Isabelle Radford-Weiss, Christine Lefebvre, Sandra Fert-Ferrer, Evelyne Callet-Bauchu, Eric Lippert, Victoria Raggueneau, Lucienne Michaux, Carole Barin, Marie-Agnes Collonge-Rame, Francine Mugneret, Virginie Eclache, Sylvie Taviaux, Nicole Dastugue, Steven Richebourg, Stéphanie Struski, Pascaline Talmant, Laurence Baranger, Nathalie Gachard, Carine Gervais, Benoit Quilichini, Catherine Settegrana, Karim Maloum, Frederic Davi, Hélène Merle-Béral.   

Abstract

BACKGROUND: 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). DESIGNS AND METHODS: 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).
RESULTS: 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).
CONCLUSIONS: 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.

Entities:  

Keywords:  BCL2; Chronic lymphocytic leukemia; IGH; chromosomal translocation

Year:  2011        PMID: 22432063      PMCID: PMC3301415     

Source DB:  PubMed          Journal:  Am J Blood Res        ISSN: 2160-1992


  20 in total

Review 1.  The role of immunoglobulin translocations in the pathogenesis of B-cell malignancies.

Authors:  T G Willis; M J Dyer
Journal:  Blood       Date:  2000-08-01       Impact factor: 22.113

2.  Translocation t(14;18) is not associated with inferior outcome in chronic lymphocytic leukemia.

Authors:  N Put; P Meeus; B Chatelain; K Rack; N Boeckx; F Nollet; C Graux; E Van Den Neste; A Janssens; V Madoe; A Van Hoof; C Bilhou-Nabera; I Wlodarska; P Vandenberghe; L Michaux
Journal:  Leukemia       Date:  2009-03-19       Impact factor: 11.528

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

Authors:  E Chapiro; I Radford-Weiss; C Bastard; I Luquet; C Lefebvre; E Callet-Bauchu; D Leroux; P Talmant; M-J Mozziconacci; F Mugneret; S Struski; S Raynaud; J Andrieux; C Barin; M Jotterand; H Mossafa; S Ramond; C Terré; E Lippert; F Berger; P Felman; H Merle-Béral; O A Bernard; F Davi; R Berger; F Nguyen-Khac
Journal:  Leukemia       Date:  2008-05-01       Impact factor: 11.528

4.  Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgV(H) status and immunophenotyping.

Authors:  C Haferlach; F Dicker; S Schnittger; W Kern; T Haferlach
Journal:  Leukemia       Date:  2007-09-06       Impact factor: 11.528

5.  Age at diagnosis and the utility of prognostic testing in patients with chronic lymphocytic leukemia.

Authors:  Tait D Shanafelt; Kari G Rabe; Neil E Kay; Clive S Zent; Diane F Jelinek; Megan S Reinalda; Susan M Schwager; Debbie A Bowen; Susan L Slager; Curtis A Hanson; Timothy G Call
Journal:  Cancer       Date:  2010-10-15       Impact factor: 6.860

6.  The B cell antigen receptor in atypical chronic lymphocytic leukemia with t(14;19)(q32;q13) demonstrates remarkable stereotypy.

Authors:  Carmen D Schweighofer; Yang O Huh; Rajyalakshmi Luthra; Rachel L Sargent; Rhett P Ketterling; Ryan A Knudson; Lynn L Barron; L Jeffrey Medeiros; Michael J Keating; Lynne V Abruzzo
Journal:  Int J Cancer       Date:  2010-10-26       Impact factor: 7.396

Review 7.  t(14;19)/BCL3 rearrangements in lymphoproliferative disorders: a review of 23 cases.

Authors:  L Michaux; J Dierlamm; I Wlodarska; V Bours; H Van den Berghe; A Hagemeijer
Journal:  Cancer Genet Cytogenet       Date:  1997-03

8.  A different ontogenesis for chronic lymphocytic leukemia cases carrying stereotyped antigen receptors: molecular and computational evidence.

Authors:  N Darzentas; A Hadzidimitriou; F Murray; K Hatzi; P Josefsson; N Laoutaris; C Moreno; A Anagnostopoulos; J Jurlander; A Tsaftaris; N Chiorazzi; C Belessi; P Ghia; R Rosenquist; F Davi; K Stamatopoulos
Journal:  Leukemia       Date:  2009-09-17       Impact factor: 11.528

9.  Chromosome 14q32 translocations involving the immunoglobulin heavy chain locus in chronic lymphocytic leukaemia identify a disease subset with poor prognosis.

Authors:  Francesco Cavazzini; Jose Angel Hernandez; Alessandro Gozzetti; Antonella Russo Rossi; Cristiano De Angeli; Ruana Tiseo; Antonella Bardi; Elisa Tammiso; Rosaria Crupi; Maria Pia Lenoci; Francesco Forconi; Francesco Lauria; Roberto Marasca; Rossana Maffei; Giuseppe Torelli; Marcos Gonzalez; Patricia Martin-Jimenez; Jesus Maria Hernandez; Gian Matteo Rigolin; Antonio Cuneo
Journal:  Br J Haematol       Date:  2008-06-28       Impact factor: 6.998

10.  A comprehensive genetic and histopathologic analysis identifies two subgroups of B-cell malignancies carrying a t(14;19)(q32;q13) or variant BCL3-translocation.

Authors:  J I Martín-Subero; R Ibbotson; W Klapper; L Michaux; E Callet-Bauchu; F Berger; M J Calasanz; C De Wolf-Peeters; M J Dyer; P Felman; A Gardiner; R D Gascoyne; S Gesk; L Harder; D E Horsman; M Kneba; R Küppers; A Majid; N Parry-Jones; M Ritgen; M Salido; F Solé; G Thiel; H-H Wacker; D Oscier; I Wlodarska; R Siebert
Journal:  Leukemia       Date:  2007-05-10       Impact factor: 11.528

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  4 in total

1.  IGH translocations in chronic lymphocytic leukemia: Clinicopathologic features and clinical outcomes.

Authors:  Hong Fang; Kaaren K Reichard; Kari G Rabe; Curtis A Hanson; Timothy G Call; Wei Ding; Saad S Kenderian; Eli Muchtar; Susan M Schwager; Jose F Leis; Asher A Chanan-Khan; Susan L Slager; Esteban Braggio; Stephanie A Smoley; Neil E Kay; Tait D Shanafelt; Daniel L Van Dyke; Sameer A Parikh
Journal:  Am J Hematol       Date:  2019-01-08       Impact factor: 10.047

Review 2.  The biology and clinical significance of acquired genomic copy number aberrations and recurrent gene mutations in chronic lymphocytic leukemia.

Authors:  S N Malek
Journal:  Oncogene       Date:  2012-09-24       Impact factor: 9.867

3.  Identification of novel, clonally stable, somatic mutations targeting transcription factors PAX5 and NKX2-3, the epigenetic regulator LRIF1, and BRAF in a case of atypical B-cell chronic lymphocytic leukemia harboring a t(14;18)(q32;q21).

Authors:  Bénédicte Burlet; Selim Ramla; Cyril Fournier; Maria Jimena Abrey-Recalde; Camille Sauter; Marie-Lorraine Chrétien; Cédric Rossi; Yannis Duffourd; Sylviane Ragot; Céline Buriller; Benjamin Tournier; Caroline Chapusot; Nathalie Nadal; Jessica Racine; Julien Guy; François Bailly; Laurent Martin; Olivier Casasnovas; Jean-Noël Bastie; Denis Caillot; Juliette Albuisson; Cyril Broccardo; Catherine Thieblemont; Laurent Delva; Marc Maynadié; Romain Aucagne; Mary B Callanan
Journal:  Cold Spring Harb Mol Case Stud       Date:  2021-02-19

4.  BCL3 Expression Is a Potential Prognostic and Predictive Biomarker in Acute Myeloid Leukemia of FAB Subtype M2.

Authors:  Yuna Niu; Xue Yang; Yifei Chen; Linbo Zhang; Xinyue Jin; Youjing Tang; Li Li; Lu Yu; Yilin Guo; Hui Wang
Journal:  Pathol Oncol Res       Date:  2018-10-25       Impact factor: 3.201

  4 in total

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