High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder.
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.
Preudhomme
Claude
C
Department of Hematology, Biology and Pathology Center, Centre Hospitalier Régional Universitaire (CHRU) of Lille, Lille, France.
Renneville
Aline
A
Bourdon
Violaine
V
Philippe
Nathalie
N
Roche-Lestienne
Catherine
C
Boissel
Nicolas
N
Dhedin
Nathalie
N
André
Jean-Marie
JM
Cornillet-Lefebvre
Pascale
P
Baruchel
André
A
Mozziconacci
Marie-Joelle
MJ
Sobol
Hagay
H
D000328:Adult; D001791:Blood Platelet Disorders / Q000150:complications / Q000235:genetics*; D002648:Child; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005190:Family; D005260:Female; D005787:Gene Frequency; D006720:Homozygote; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011230:Precancerous Conditions / Q000235:genetics; D055815:Young Adult
D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human