Investigation of the role of chromatin control via small temporal RNA in drag resistance of hematopoietic malignancy

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15760
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Tokyo Women's Medical University (2018); Tokyo Medical University (2017)
• Principal Investigator: Azuma Kenko 東京女子医科大学, 医学部, 助教 (80724070)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: アザシチジンによるクロマチン制御因子の発現制御 / アザシチジン耐性における新規標的

Outline of Final Research Achievements

Even though azacitidine is known as an effective agent for myelodysplastic syndrome, it is clinical problem that tumor can get drag-resistant easily against azacitidine. In this study, we focused on control of chromatin which is composed by complex of DNA and proteins, that is one of resistance mechanisms against azacitidine. We found that two important chromatin control genes, PIWIL4 and MAEL were over-expressed in azacitidine-resistant cells constantly against azacitidine-sensitive cells. Most especially, PIWIL4 was susceptible to azacitidine specifically in azacitidine-sensitive cells. As a result, the possibility of the function of PIWIL4 which may contributes to acquisition of resistance is higher, and it indicates that PIWIL4 could be a novel molecular target of azacitidine-resistant tumors.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

薬剤耐性はガンの化学療法において重要な問題となっている。本研究は「血液のガン」の一つである骨髄異形成症候群という疾患で重要な治療薬であるアザシチジンに着目した。アザシチジンは有効性が高い反面、確実に耐性獲得することが臨床上の問題となっている。本研究の成果として、アザシチジンの耐性機序に関与する因子を特定したことから、耐性獲得後の治療のための新しい分子標的を提示することができた。