RUNX1 deficiency (familial platelet disorder with predisposition to myeloid leukemia, FPDMM)
RUNX1 deficiency (familial platelet disorder with predisposition to myeloid leukemia, FPDMM)
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DOI：
10.1053/j.seminhematol.2017.04.006
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发表时间：
2017-04-01
影响因子：
3.6
通讯作者：
Heller, Paula G.
中科院分区：
文献类型：
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作者：
Schlegelberger, Brigitte;Heller, Paula G.
在这篇综述中，我们讨论了矮小相关转录因子1(RUNX1)的致病变化，RUNX1是造血分化的主要调节因子。易感于髓系白血病的家族性血小板紊乱(FPDMM)通常表现为(1)轻度至中度血小板减少，血小板大小正常；(2)功能性血小板缺陷导致长期出血；(3)发展为骨髓增生异常综合征(MDS)、急性髓系白血病(AML)或T细胞急性淋巴细胞白血病(T-ALL)的风险增加。生殖系RUNX1突变携带者中的血液肿瘤需要额外的继发性突变或染色体异常才能发展。如果家族中已知导致突变的疾病，重要的是防止携带家族突变的兄弟姐妹或其他亲属进行造血干细胞移植。首先，将野生型RUNX1复制到来自FPDMM患者的诱导多能干细胞(IPSC)系中的实验似乎表明，通过基因纠正，表型逆转是可能的。(C)爱思唯尔公司出版的2017年。
In this review, we discuss disease-causing alterations of RUNT-related transcription factor 1 (RUNX1), a master regulator of hematopoietic differentiation. Familial platelet disorder with predisposition to myeloid leukemia (FPDMM) typically presents with (1) mild to moderate thrombocytopenia with normal-sized platelets; (2) functional platelets defects leading to prolonged bleeding; and (3) an increased risk to develop myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), or T-cell acute lymphoblastic leukemia (T-ALL). Hematological neoplasms in carriers of a germline RUNX1 mutation need additional secondary mutations or chromosome aberrations to develop. If a disease causing mutation is known in the family, it is important to prevent hematopoietic stem cell transplantation from a sibling or other relative carrying the familial mutation. First experiments introducing a wild-type copy of RUNX1 into induce pluripotent stem cells (iPSC) lines from patients with FPDMM appear to demonstrate that by gene correction reversal of the phenotype may be possible. (C) 2017 Published by Elsevier Inc.