High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder

被引:143
作者
Preudhomme, Claude [2 ,3 ]
Renneville, Aline [2 ,3 ]
Bourdon, Violaine
Philippe, Nathalie [2 ,3 ]
Roche-Lestienne, Catherine [4 ]
Boissel, Nicolas [5 ]
Dhedin, Nathalie [6 ]
Andre, Jean-Marie [7 ]
Cornillet-Lefebvre, Pascale [8 ]
Baruchel, Andre [9 ]
Mozziconacci, Marie-Joelle
Sobol, Hagay [1 ]
机构
[1] Inst J Paoli I Calmettes, Dept Gen Oncol, Inserm CIC P9502, Oncol & Immunol Inst Marseille IFR 137, F-13273 Marseille 9, France
[2] CHRU, Dept Hematol Biol & Pathol Ctr, Lille, France
[3] NW Cancerpole, Rouen, France
[4] CHRU Lille, Jeanne Flandres Hosp, Dept Med Genet, Lille, France
[5] Hop St Louis, Dept Adult Hematol, Paris, France
[6] Hop La Pitie Salpetriere, Dept Clin Hematol, Paris, France
[7] Debrousse Hosp, Dept Pediat Oncohematol, Lyon, France
[8] CHRU Reims, Hematol Lab, Reims, France
[9] Hop Robert Debre, Dept Pediat Hematol, F-75019 Paris, France
关键词
ACUTE MYELOGENOUS LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; RAS GENE-MUTATIONS; TANDEM DUPLICATION; CEBPA MUTATIONS; PROPENSITY; FLT3; MALIGNANCIES; HAPLOINSUFFICIENCY; THROMBOCYTOPENIA;
D O I
10.1182/blood-2008-07-168260
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (Blood. 2009; 113: 5583-5587)
引用
收藏
页码:5583 / 5587
页数:5
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