High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder
High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder
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DOI：
10.1182/blood-2008-07-168260
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发表时间：
2009-05-28
期刊：
影响因子：
20.3
通讯作者：
Sobol, Hagay
中科院分区：
文献类型：
--
作者：
Preudhomme, Claude;Renneville, Aline;Sobol, Hagay
家族性血小板疾病（FPD）是一种以血小板数量和质量异常为特征的罕见常染色体显性遗传疾病，被认为是急性髓系白血病（AML）的遗传易感性模型。到目前为止，在20个报告的FPD家族中有19个发现了单等位基因RUNX 1种系突变，并且仅对5名急性白血病（AL）期患者的原始细胞进行分析，未发现额外的RUNX 1异常。在这里，我们对来自4个独立家庭的8名患AL的FPD患者进行了体质和身体水平的RUNX 1分析。除了生殖系RUNX 1突变，我们在6例AML病例中发现了第二个RUNX 1改变（4例获得性点突变，2例获得性21三体相关的RUNX 1等位基因重复）。尽管RUNX 1的单倍不足导致FPD，但我们的研究结果表明，涉及RUNX 1的第二个遗传事件通常与AML的进展相关。（血。2009; 113：5583-5587）
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)