title: 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.
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.
authors: INSERM U563, Toulouse, France.
authors: J
authors: J
authors: Familiades
authors: M
authors: M
authors: Bousquet
authors: M
authors: M
authors: Lafage-Pochitaloff
authors: M-C
authors: MC
authors: Béné
authors: K
authors: K
authors: Beldjord
authors: J
authors: J
authors: De Vos
authors: N
authors: N
authors: Dastugue
authors: E
authors: E
authors: Coyaud
authors: S
authors: S
authors: Struski
authors: C
authors: C
authors: Quelen
authors: N
authors: N
authors: Prade-Houdellier
authors: S
authors: S
authors: Dobbelstein
authors: J-M
authors: JM
authors: Cayuela
authors: J
authors: J
authors: Soulier
authors: N
authors: N
authors: Grardel
authors: C
authors: C
authors: Preudhomme
authors: H
authors: H
authors: Cavé
authors: O
authors: O
authors: Blanchet
authors: V
authors: V
authors: Lhéritier
authors: A
authors: A
authors: Delannoy
authors: Y
authors: Y
authors: Chalandon
authors: N
authors: N
authors: Ifrah
authors: A
authors: A
authors: Pigneux
authors: P
authors: P
authors: Brousset
authors: E A
authors: EA
authors: Macintyre
authors: F
authors: F
authors: Huguet
authors: H
authors: H
authors: Dombret
authors: C
authors: C
authors: Broccardo
authors: E
authors: E
authors: Delabesse
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001549:Benzamides; D017322:Clinical Trials, Phase II as Topic; D004268:DNA-Binding Proteins / Q000235:genetics*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D018628:Gene Dosage; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D023281:Genomics; D006239:Haplotypes; D006801:Humans; D000068877:Imatinib Mesylate; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D016130:Immunophenotyping; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D051757:PAX5 Transcription Factor / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use; D017354:Point Mutation; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D051792:Basic Helix-Loop-Helix Proteins; D001549:Benzamides; D004268:DNA-Binding Proteins; D016044:Fusion Proteins, bcr-abl; D000068877:Imatinib Mesylate; D007143:Immunoglobulin Heavy Chains; D051757:PAX5 Transcription Factor; D010879:Piperazines; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines; C497281:PAX5 protein, human; C407909:TCF3 protein, human; C083400:PBX1 protein, human