A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies
A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies
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DOI：
10.1182/blood.v98.9.2856
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发表时间：
2001-11-01
期刊：
影响因子：
20.3
通讯作者：
Lokhorst, H
中科院分区：
文献类型：
--
作者：
Buijs, A;Poddighe, P;Lokhorst, H
与血液系统恶性肿瘤相关的遗传性突变是罕见的。影响造血转录因子CBFA 2（也称为AML 1/RUNX 1）的杂合突变最近被报道与家族性血小板疾病伴急性髓性白血病易感性相关（FPD/AML，MIM 601399）。描述了一个新的3代FPD/AML家族，该家族具有新的CBFA 2突变。在这个家庭中，AML被诊断为第二代男性。在从他的人类白细胞抗原相同的姐姐移植异基因干细胞后，受体和供体发生了供体来源的遗传相同的白血病。测序分析发现CBFA 2基因内存在G到T的转变，该转变涉及密码子198，编码DNA结合Runt结构域内的保守天冬氨酸。受FPD/AML性状影响的5个兄弟姐妹中有3个以杂合形式携带突变。这一经验强调了在FPD/AML家族中进行同胞异基因移植前对CBFA 2基因进行突变分析的必要性。(C)2001年，美国血液学会。
Hereditary mutations associated with hematologic malignancies are rare. Heterozygous mutations affecting the hematopoietic transcription factor CBFA2 (also AML1/RUNX1) were recently reported to be associated with familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML, MIM 601399). A new 3-generation family with FPD/AML with a novel CBFA2 mutation is described. In this family, AML was diagnosed in a second-generation male. After allogeneic stem cell transplantation from his human leukocyte antigen-identical sister, a donor-derived, genetically identical leukemia developed in the recipient and the donor. Sequencing analysis identified a G-to-T transition within the CBFA2 gene, which involves codon 198, encoding a conserved aspartic acid within the DNA-binding Runt domain. Three of 5 siblings affected with the FPD/AML trait harbored the mutation in a heterozygous form. This experience underscores the necessity of performing mutation analysis of the CBFA2 gene before sibling allogeneic transplantation in families with FPD/AML. (C) 2001 by The American Society of Hematology.