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PAX5 mutations occur frequently in adult B-cell progenitor acute lymphoblastic leukemia and PAX5 haploinsufficiency is associated with BCR-ABL1 and TCF3-PBX1 fusion genes: a GRAALL study

Authors
Familiades, J
Bousquet, M
Lafage-Pochitaloff, M
Béné, M-C
Beldjord, K
De Vos, J
Dastugue, N
Coyaud, E
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Published in Leukemia. 2009, vol. 23, no. 11, p. 1989-98
Abstract Adult and child B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) differ in terms of incidence and prognosis. These disparities are mainly due to the molecular abnormalities associated with these two clinical entities. A genome-wide analysis using oligo SNP arrays recently demonstrated that PAX5 (paired-box domain 5) is the main target of somatic mutations in childhood BCP-ALL being altered in 38.9% of the cases. We report here the most extensive analysis of alterations of PAX5 coding sequence in 117 adult BCP-ALL patients in the unique clinical protocol GRAALL-2003/GRAAPH-2003. Our study demonstrates that PAX5 is mutated in 34% of adult BCP-ALL, mutations being partial or complete deletion, partial or complete amplification, point mutation or fusion gene. PAX5 alterations are heterogeneous consisting in complete loss in 17%, focal deletions in 10%, point mutations in 7% and translocations in 1% of the cases. PAX5 complete loss and PAX5 point mutations differ. PAX5 complete loss seems to be a secondary event and is significantly associated with BCR-ABL1 or TCF3-PBX1 fusion genes and a lower white blood cell count.
Keywords AdolescentAdultAntineoplastic Agents/therapeutic useB-Cell-Specific Activator Protein/geneticsBasic Helix-Loop-Helix Transcription Factors/geneticsClinical Trials, Phase II as TopicDNA-Binding Proteins/geneticsFusion Proteins, bcr-abl/geneticsGene DosageGene Rearrangement, T-Lymphocyte/geneticsGenomicsHaplotypesHumansImmunoglobulin Heavy Chains/geneticsImmunophenotypingMiddle AgedMulticenter Studies as TopicPiperazines/therapeutic usePoint MutationPrecursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/geneticsPrognosisProspective StudiesProto-Oncogene Proteins/geneticsPyrimidines/therapeutic useYoung Adult
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PMID: 19587702
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FAMILIADES, J et al. PAX5 mutations occur frequently in adult B-cell progenitor acute lymphoblastic leukemia and PAX5 haploinsufficiency is associated with BCR-ABL1 and TCF3-PBX1 fusion genes: a GRAALL study. In: Leukemia, 2009, vol. 23, n° 11, p. 1989-98. https://archive-ouverte.unige.ch/unige:25875

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Deposited on : 2013-01-23

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