Molecular pathogenesis in myelodysplastic syndromes (MDS).

2018 Fiscal Year Final Research Report

• Project/Area Number: 26221308
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Kyoto University
• Principal Investigator: OGAWA SEISHI 京都大学, 医学研究科, 教授 (60292900)
• Co-Investigator(Kenkyū-buntansha): 古関 明彦 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (40225446)
• Research Collaborator: Sanada Masashi ; Sato Aiko ; Makishima Hideki ; Kataoka Keisuke ; Miyazaki Yasushi ; Chiba Shigeru ; Nakao Shinji ; Nakauchi Hiromitsu ; Nakayama Manabu
• Project Period (FY): 2014-05-30 – 2019-03-31
• Keywords: 血液内科学 / 血液腫瘍学 / 骨髄異形成症候群

Outline of Final Research Achievements

On the basis of our previous identification of genetic mutations, we planned to clarify pathophysiology in myelodysplastic syndromes (MDS) associated with combinations of such mutations. Using next generation sequencing technology and mouse models, we elucidated genetic and biological process of acquiring survival benefit, relating to hematopoietic environment, and initiating secondary leukemia from MDS. Of note, we comprehensively uncovered that such pathogenic process was resulted not from a single genetic event but combination of mutations and that such combination was not random and significantly associated with the order of acquiring each mutation. These findings suggest that clonal expansion in MDS is closely related to various genetic events but specific rules strictly controlled by environmental condition.

Free Research Field

悪性腫瘍のゲノム解析

Academic Significance and Societal Importance of the Research Achievements

骨髄異形成症候群(MDS)およびその関連疾患は、骨髄形成不全と急性骨髄性白血病への進展を特徴とする、高齢者に好発する慢性骨髄性腫瘍である。MDSの主な死因である骨髄不全および急性白血病に関して、本研究課題では、全研究機関を通じて、全ゲノムおよびRNAシーケンスを含む世界トップレベルの遺伝子解析技術とマウスモデルを駆使した手法を用いて、多様な遺伝子変異がMDSを発症させ、MDSを白血病へ進展させるメカニズムについて明らかにした。以上の研究成果は、学会発表をへて、現在論文化の予定である。