Overexpression of RUNX1 short isoform induced by epigenetic dysregulation in the development of myelodysplastic/myeloproliferative neoplasms (MDS/MPN)

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Tokyo University of Pharmacy and Life Science (2016-2017); Juntendo University (2015)
• Principal Investigator: Harada Hironori 東京薬科大学, 生命科学部, 教授 (10314775)
• Co-Investigator(Kenkyū-buntansha): 原田 結花 文京学院大学, 保健医療技術学部, 教授 (50379848)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: RUNX1 / 慢性骨髄単球性白血病（CMML） / MDS/MPN / スプライシング因子 / BMTモデル

Outline of Final Research Achievements

RUNX1 mutations have been shown to contribute to the development of myeloid neoplasms and are frequently identified in patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN) including chronic monocytic leukemia (CMML). The RUNX1 gene has several isoforms. We focused on both functional full-length isoforms RUNX1b and the short isoform RUNX1a. RUNX1a has a dominant negative effect on RUNX1b. We quantified expression levels of RUNX1 isoforms in CD34+ cells from patients with MDS/MPN. We found that RUNX1a was overexpressed in MDS/MPN patients, and that these levels of expression increased as the disease progressed. Furthermore, the aberrant splicing resulting in RUNX1a was shown to be caused by splicing factor mutations that are frequently detected in MDS/MPN. We demonstrated for the first time that in addition to RUNX1 mutations, overexpression of RUNX1a induced by splicing factor mutations may have an important role in disease progression in MDS/MPN patients.

Free Research Field

血液内科学