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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

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Familiades, J. De Vos, Julien [UCL] Delannoy, André [UCL]

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. Leukemia (2009) 23, 1989-1998; doi: 10.1038/leu.2009.135; published online 9 July 2009

Document type Article de périodique (Journal article) – Article de recherche
Publication date 2009
Language Anglais
Journal information "Leukemia" - Vol. 23, no. 11, p. 1989-1998 (2009)
Peer reviewed yes
Publisher Nature Publishing Group (London)
issn 0887-6924
e-issn 1476-5551
Publication status Publié
Affiliation UCL
Keywords BCP-ALL ; oncogenesis ; BCR-ABL1 ; PAX5 ; TCF3-PBX1
Links
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Bibliographic reference Familiades, J. ; De Vos, Julien ; Delannoy, André ; 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, Vol. 23, no. 11, p. 1989-1998 (2009)
Permanent URL http://hdl.handle.net/2078.1/35164