Understanding the molecular mechanisms through histone acetyl-transferase in the differentiation therapy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16099
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Juntendo University
• Principal Investigator: Shirane Shuichi 順天堂大学, 医学部, 助教 (40760129)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 急性前骨髄性白血病 / ATRA / ヒストンアセチル基転移酵素 / 分化誘導療法

Outline of Final Research Achievements

This study aimed to comprehensively elucidate the transcriptional network regulated by a differentiation-inducing reagent and to clarify the involvement of histone acetyltransferases in the differentiation, which will contribute to the establishment of basis for the development of differentiation-inducing therapies that can be applied to the treatment of a wider range of cancers. This study revealed a group of genes involved in the process of differentiation of acute promyelocytic leukemia cells into neutrophils by all-transretinoic acid (ATRA), which is used clinically as differentiation-inducing drugs for hematological malignancies. Furthermore, the role of histone acetyltransferases, which are involved in the regulation of the expression of a wide range of genes among these genes, in ATRA-induced neutrophil differentiation was clarified.

Free Research Field

血液内科

Academic Significance and Societal Importance of the Research Achievements

本研究により明らかになった分化誘導性遺伝子の候補を検索することで、今後、広範な腫瘍に効果的な分化誘導薬の開発が期待される。これにより、副作用の強い化学療法剤に代わる分化誘導薬が、急性前骨髄球性白血病以外の腫瘍においても開発されれば、抗がん剤の選択肢が増えるだけでなく、がん患者のQOL向上に結びつくことなどから、本研究の成果は学術的にも社会的にも極めて意義深いと言える。