Molecular mechanisms of radiation-associated myelodysplastic syndromes (MDS)

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461422
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Bunkyo Gakuin University (2015); Juntendo University (2013-2014)
• Principal Investigator: HARADA Yuka 文京学院大学, 保健医療学部, 教授 (50379848)
• Co-Investigator(Kenkyū-buntansha): HARADA Hironori 順天堂大学, 医学部, 准教授 (10314775)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 低線量被曝 / RUNX1変異 / 骨髄異形成症候群 / 骨髄異形成／骨髄増殖性腫瘍 / 慢性骨髄単球性白血病 / スプライシング因子変異

Outline of Final Research Achievements

We analyzed gene mutations in patients with myeloid neoplasms mainly myelodysplastic syndromes (MDS) including atomic bomb survivors in Hiroshima. Low dose radiation-associated MDS patients showed slightly higher frequency of RUNX1 mutations than the patients within 2 km from hypocenter. Especially, both of 2 patients exposed to “black rain”, which contains radioactive fallout just after atomic bomb in Hiroshima, developed chronic myelomonocytic leukemia (CMML) with RUNX1 mutations. Therefore, we investigated gene abnormalities in CMML patients and found high frequency of RUNX1 mutations. Furthermore, high expression of RUNX1 short isoform (RUNX1a) was associated with mutations of splicesome factors which were frequently found in CMML. It is suspected that RUNX1 mutations may be induced by low dose radiation. In addition, hematopoietic stem cells with RUNX1 mutations may have resistance to irradiation and proliferate after radiation injury.

Free Research Field

血液内科学