Abstract：
DIAPH1, a member of the formins family and a Rho effector, was found to be involved in thrombocytopoiesis, and the process of MDS in mice with unknown pathogenesis. In this study, we reported a preliminary study about the heterogeneity in the clinical features and outcomes of DIAPH1 mutations in MDS. DIAPH1 frameshift mutations were identified in 20 out of 88 MDS patients, including 11 frameshift mutations locating at 140892588-141000567 (5q31.3), which causes structure changes at FH1 domain. DIAPH1 mutated cases were correlated with lower megakaryocyte dysplasia in lower-risk patients (IPSS-M score <0) at first diagnosis, and higher megakaryocyte counts pre-transplant. The megakaryopoiesis-related genes: GP1BA and SETBP1 mutation were positively and negatively associated with DIAPH1 mutation, respectively. DIAPH1 mutated cases showed superior overall survival of all patients and low-risk cohorts. In conclusion, we found DIAPH1 frameshift mutations are implicated in megakaryopoiesis of MDS and correlated with superior prognosis.
摘要：
DIAPH1是Formins家族的成员和Rho效应子，被发现与血小板生成有关,以及在发病机制未知的小鼠中MDS的过程。在这项研究中,我们报道了一项关于MDS患者DIAPH1突变的临床特征和结局异质性的初步研究.在88例MDS患者中，有20例发现了DIAPH1移码突变，包括11个移码突变，位于140892588~141000567(5q31.3)，这导致FH1域的结构变化。在首次诊断时，DIAPH1突变病例与低风险患者的下巨核细胞发育不良相关（IPSS-M评分<0）（P=0.031），移植前巨核细胞计数较高（P=0.033）。巨核细胞生成相关基因:GP1BA和SETBP1突变与DIAPH1突变呈正相关和负相关,分别。DIAPH1突变病例显示所有患者（P=0.037）和低风险队列（P=0.049）的总生存率较高。总之,我们发现DIAPH1移码突变与MDS的巨核细胞生成有关,并与预后良好相关.
