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 | Bousquet, M | Lafage-Pochitaloff, M | Béné, M-C | Beldjord, K | De Vos, J | Dastugue, N | Coyaud, E | Struski, S | Quelen, C | Prade-Houdellier, N | Dobbelstein, S | Cayuela, J-M | Soulier, J | Grardel, N | Preudhomme, C | Cavé, H | Blanchet, O | Lhéritier, V | Delannoy, A | Chalandon, Y | Ifrah, N | Pigneux, A | Brousset, P | Macintyre, E | Huguet, F | Dombret, H | Broccardo, C | Delabesse, É

Edité par CCSD ; Springer Nature -

International audience. 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.

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