BACKGROUND: Recently, in genome-wide analyses of DNA copy number abnormalities using single nucleotide polymorphism microarrays, genetic alterations targeting PAX5 were identified in over 30% of pediatric patients with acute lymphoblastic leukemia. So far the occurrence of PAX5 alterations and their clinical correlation have not been investigated in adults with BCR-ABL1-positive acute lymphoblastic leukemia. DESIGN AND METHODS: The aim of this study was to characterize the rearrangements on 9p involving PAX5 and their clinical significance in adults with BCR-ABL1-positive acute lymphoblastic leukemia. Eighty-nine adults with de novo BCR-ABL1-positive acute lymphoblastic leukemia were enrolled into institutional (n=15) or GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) (n=74) clinical trials and, after obtaining informed consent, their genome was analyzed by single nucleotide polymorphism arrays (Affymetrix 250K NspI and SNP 6.0), genomic polymerase chain reaction analysis and re-sequencing. RESULTS: PAX5 genomic deletions were identified in 29 patients (33%) with the extent of deletions ranging from a complete loss of chromosome 9 to the loss of a subset of exons. In contrast to BCR-ABL1-negative acute lymphoblastic leukemia, no point mutations were found, suggesting that deletions are the main mechanism of inactivation of PAX5 in BCR-ABL1-positive acute lymphoblastic leukemia. The deletions were predicted to result in PAX5 haploinsufficiency or expression of PAX5 isoforms with impaired DNA-binding. Deletions of PAX5 were not significantly correlated with overall survival, disease-free survival or cumulative incidence of relapse, suggesting that PAX5 deletions are not associated with outcome. CONCLUSIONS: PAX5 deletions are frequent in adult BCR-ABL1-positive acute lymphoblastic leukemia and are not associated with a poor outcome.
BACKGROUND: Recently, in genome-wide analyses of DNA copy number abnormalities using single nucleotide polymorphism microarrays, genetic alterations targeting PAX5 were identified in over 30% of pediatric patients with acute lymphoblastic leukemia. So far the occurrence of PAX5 alterations and their clinical correlation have not been investigated in adults with BCR-ABL1-positive acute lymphoblastic leukemia. DESIGN AND METHODS: The aim of this study was to characterize the rearrangements on 9p involving PAX5 and their clinical significance in adults with BCR-ABL1-positive acute lymphoblastic leukemia. Eighty-nine adults with de novo BCR-ABL1-positive acute lymphoblastic leukemia were enrolled into institutional (n=15) or GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) (n=74) clinical trials and, after obtaining informed consent, their genome was analyzed by single nucleotide polymorphism arrays (Affymetrix 250K NspI and SNP 6.0), genomic polymerase chain reaction analysis and re-sequencing. RESULTS:PAX5 genomic deletions were identified in 29 patients (33%) with the extent of deletions ranging from a complete loss of chromosome 9 to the loss of a subset of exons. In contrast to BCR-ABL1-negative acute lymphoblastic leukemia, no point mutations were found, suggesting that deletions are the main mechanism of inactivation of PAX5 in BCR-ABL1-positive acute lymphoblastic leukemia. The deletions were predicted to result in PAX5haploinsufficiency or expression of PAX5 isoforms with impaired DNA-binding. Deletions of PAX5 were not significantly correlated with overall survival, disease-free survival or cumulative incidence of relapse, suggesting that PAX5 deletions are not associated with outcome. CONCLUSIONS:PAX5 deletions are frequent in adult BCR-ABL1-positive acute lymphoblastic leukemia and are not associated with a poor outcome.
Authors: Qian An; Sarah L Wright; Zoë J Konn; Elizabeth Matheson; Lynne Minto; Anthony V Moorman; Helen Parker; Mike Griffiths; Fiona M Ross; Teresa Davies; Andy G Hall; Christine J Harrison; Julie A Irving; Jon C Strefford Journal: Proc Natl Acad Sci U S A Date: 2008-10-28 Impact factor: 11.205
Authors: Norihiko Kawamata; Seishi Ogawa; Martin Zimmermann; Birte Niebuhr; Carol Stocking; Masashi Sanada; Kari Hemminki; Go Yamatomo; Yasuhito Nannya; Rolf Koehler; Thomas Flohr; Carl W Miller; Jochen Harbott; Wolf-Dieter Ludwig; Martin Stanulla; Martin Schrappe; Claus R Bartram; H Phillip Koeffler Journal: Proc Natl Acad Sci U S A Date: 2008-08-12 Impact factor: 11.205
Authors: J Familiades; M Bousquet; M Lafage-Pochitaloff; M-C Béné; K Beldjord; J De Vos; N Dastugue; E Coyaud; S Struski; C Quelen; N Prade-Houdellier; S Dobbelstein; J-M Cayuela; J Soulier; N Grardel; C Preudhomme; H Cavé; O Blanchet; V Lhéritier; A Delannoy; Y Chalandon; N Ifrah; A Pigneux; P Brousset; E A Macintyre; F Huguet; H Dombret; C Broccardo; E Delabesse Journal: Leukemia Date: 2009-07-09 Impact factor: 11.528