Submitted July 14, 2008
Accepted April 2, 2009
High frequency of RUNX1 bi-allelic alteration in acute myeloid leukemia (AML) secondary to familial platelet disorder (FPD)
Claude Preudhomme, Aline Renneville, Violaine Bourdon, Nathalie Philippe, Catherine Roche-Lestienne, Nicolas Boissel, Nathalie Dhedin, Jean-Marie Andre, Pascale Cornillet-Lefebvre, Andre Baruchel, Marie-Joelle Mozziconacci, and Hagay Sobol*
Department of Hematology, Biology and Pathology Center, CHRU of Lille, Lille, France
Department of Genetic Oncology, Paoli Calmettes Institute, Marseille, France
Department of Medical Genetics, Jeanne de Flandres Hospital, CHRU of Lille, Lille, France
Department of Adult Hematology, Saint-Louis Hospital, Paris, France
Department of Clinical Hematology, La Pitie-Salpetriere Hospital, Paris, France
Department of Pediatric Onco-Hematology, Debrousse Hospital, Lyon, France
Hematology Laboratory, CHRU of Reims, Reims, France
Department of Pediatric Hematology, Robert Debre Hospital, Paris, France
* Corresponding author; email: hagay.sobol{at}inserm.fr.
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 germ-line mutations have been found in 19 out of 20 reported FPD families and the analysis of blast cells from only 5 patients at acute leukemia (AL) stage has revealed no additional RUNX1 abnormality. Here, we performed RUNX1 analysis at constitutional and somatic levels in 8 FPD individuals who developed AL from 4 independent families. In addition to the germ-line 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). While haploinsufficiency of RUNX1 causes FPD, our findings suggest that a second genetic event involving RUNX1 is often associated with progression to AML.
