Fiche publication
Date publication
mai 2009
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CORNILLET-LEFEBVRE Pascale
Tous les auteurs :
Preudhomme C, Renneville A, Bourdon V, Philippe N, Roche-Lestienne C, Boissel N, Dhedin N, Andre JM, Cornillet-Lefebvre P, Baruchel A, Mozziconacci MJ, Sobol H
Lien Pubmed
Résumé
Familial platelet disorder (FPD), a rare autosomal dominant disorder characterized by quantitative and qualitative platelet abnormalities, is considered as a model of genetic predisposition to acute myeloid leukemia (AML). So far, monoallelic RUNX1 germline mutations have been found in 19 of 20 families with reported FPD, and the analysis of blast cells from only 5 patients at acute leukemia (AL) stage has shown no additional RUNX1 abnormality. Here, we performed RUNX1 analysis at constitutional and somatic levels in 8 persons with FPD who developed AL from 4 independent families. In addition to the germline RUNX1 mutation, we identified a second RUNX1 alteration in 6 AML cases (acquired point mutations in 4 cases and duplication of the altered RUNX1 allele associated with acquired trisomy 21 in 2 other cases). Although haploinsufficiency of RUNX1 causes FPD, our findings suggest that a second genetic event involving RUNX1 is often associated with progression to AML.
Référence
Blood. 2009 May 28;113(22):5583-7
