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Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
Published on: October 3, 2018
DIAPH1 mutations predict a favorable outcome for de novo MDS
Yaqiong Tang1, Hong Wang1, Ziyan Zhang1
1National 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.
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.
Insights
DIAPH1 frameshift mutations impact megakaryopoiesis in myelodysplastic syndromes (MDS). These mutations correlate with better outcomes and superior survival rates in MDS patients, particularly in lower-risk groups.
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- DIAPH1, a formin family member and Rho effector, plays a role in thrombocytopoiesis and myelodysplastic syndromes (MDS).
- The specific role and clinical impact of DIAPH1 mutations in MDS remain incompletely understood.
Purpose of the Study:
- To investigate the heterogeneity in clinical features and outcomes associated with DIAPH1 mutations in MDS patients.
- To explore the correlation between DIAPH1 mutations and megakaryopoiesis, as well as survival in MDS.
Main Methods:
- Genomic analysis to identify DIAPH1 frameshift mutations in 88 MDS patients.
- Correlation analysis of DIAPH1 mutations with clinical parameters, including megakaryocyte dysplasia, megakaryocyte counts, and overall survival.
- Assessment of associations with other megakaryopoiesis-related genes (GP1BA, SETBP1).
Main Results:
- DIAPH1 frameshift mutations were found in 20 out of 88 MDS patients, with several located in the FH1 domain.
- DIAPH1 mutations were associated with lower megakaryocyte dysplasia and higher megakaryocyte counts in specific patient subgroups.
- DIAPH1 mutations showed a positive association with GP1BA mutations and a negative association with SETBP1 mutations.
- Patients with DIAPH1 mutations exhibited superior overall survival, especially in lower-risk MDS cohorts.
Conclusions:
- DIAPH1 frameshift mutations are implicated in the megakaryopoiesis process within MDS.
- DIAPH1 mutations serve as a potential biomarker for a superior prognosis in MDS patients.
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