National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China.
Suzhou Hongci Hematology Hospital, Suzhou, China.
Cancer Lett. 2024 Aug 28;598:217125. doi: 10.1016/j.canlet.2024.217125. Epub 2024 Jul 30.
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.
DIAPH1 是formin 家族的一员，也是 Rho 的效应物，它被发现参与了血小板生成和发病机制未知的小鼠 MDS 中。在这项研究中，我们报告了关于 DIAPH1 突变在 MDS 中的临床特征和结果异质性的初步研究。在 88 例 MDS 患者中发现了 20 例 DIAPH1 移码突变，包括 11 个位于 140892588-141000567（5q31.3）的移码突变，导致 FH1 结构域发生结构改变。DIAPH1 突变与初次诊断时较低风险患者（IPSS-M 评分<0）的巨核细胞发育不良减少有关，并且移植前巨核细胞计数较高。巨核细胞生成相关基因：GP1BA 和 SETBP1 突变与 DIAPH1 突变分别呈正相关和负相关。DIAPH1 突变病例的所有患者和低危组的总生存率均较高。总之，我们发现 DIAPH1 移码突变与 MDS 的巨核细胞生成有关，并与较好的预后相关。
