Elucidation of etiology in Diamond-Blackfan anemia focusing on the ribosomal protein genes abnormality

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07868
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Hirosaki University
• Principal Investigator: KAMIO TAKUYA 弘前大学, 医学部附属病院, 助教 (50587011)
• Co-Investigator(Kenkyū-buntansha): 土岐 力 弘前大学, 医学研究科, 講師 (50195731) ; 金崎 里香 弘前大学, 医学研究科, 助教 (60722882)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: Diamond-Blackfan貧血 / リボゾーム蛋白 / MDM2 / p53

Outline of Final Research Achievements

In Diamond-Blackfan anemia (DBA), a red blood cell hematopoietic failure mechanism is still unknown. Previously, we reported that the MDM2C305F mutation mouse, MDM2 could not be inhibited the bind to specific ribosomal proteins, caused specific red blood cells hematopoiesis failure(PLoS One. 2016). Using the murine embryo fibroblasts by performing RNA-seq, we discovered that a specific gene was associated with pure red cells aplasia with the MDM2C305F mutation mouse. Also, we sent questionnaires about the responses to therapeutic procedures, stem cell transplantation(SCT), complications, and prognosis to the physicians of the DBA patients enrolled in our cohort. In this retrospective study, we reported the success of SCT of DBA patients following reduced-intensity conditioning regimens(Bone Marrow Transplant. 2020).

Free Research Field

小児血液腫瘍

Academic Significance and Societal Importance of the Research Achievements

Diamond-Blackfan貧血 (DBA) は、乳幼児期に発症する赤芽球造血のみが障害される先天性の赤芽球癆である。約70％の症例でリボゾーム蛋白遺伝子のハプロ不全を認めるが、それがどのように赤血球の造血不全を起こすか、未だ解明されていない。
本研究は、どのような標的遺伝子の発現制御が造血不全を引き起こすのか、その分子生物学的な機構の一端が明らかとなる可能性がある。また、他の先天性造血不全症のメカニズムを解明する上でも重要な情報が得られることが予想され、先天性造血不全症の新たな治療法の発見につながるメカニズムが解明される可能性を秘める。