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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Antineoplastic Agents / therapeutic use
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Basic Helix-Loop-Helix Transcription Factors / genetics*
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Benzamides
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Clinical Trials, Phase II as Topic
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DNA-Binding Proteins / genetics*
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Fusion Proteins, bcr-abl / genetics*
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Gene Dosage
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Gene Rearrangement, T-Lymphocyte / genetics
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Genomics
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Haplotypes
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Humans
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Imatinib Mesylate
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Immunoglobulin Heavy Chains / genetics
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Immunophenotyping
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Middle Aged
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Multicenter Studies as Topic
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PAX5 Transcription Factor / genetics*
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Piperazines / therapeutic use
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Point Mutation
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Pre-B-Cell Leukemia Transcription Factor 1
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
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Prognosis
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Prospective Studies
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Proto-Oncogene Proteins / genetics*
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Pyrimidines / therapeutic use
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Young Adult
Substances
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Antineoplastic Agents
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Basic Helix-Loop-Helix Transcription Factors
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Benzamides
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DNA-Binding Proteins
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Immunoglobulin Heavy Chains
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PAX5 Transcription Factor
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PAX5 protein, human
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Piperazines
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Pre-B-Cell Leukemia Transcription Factor 1
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Proto-Oncogene Proteins
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Pyrimidines
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TCF3 protein, human
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PBX1 protein, human
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Imatinib Mesylate
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Fusion Proteins, bcr-abl