Role of Epigenomic alterations in Myeloproliferative neoplasms

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17834
• 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: University of Miyazaki
• Principal Investigator: Kamiunten Ayako 宮崎大学, 医学部, 助教 (30800750)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: MPN / ET / myelofibrosis / CALR / EZH2

Outline of Final Research Achievements

We generated CALR mutant mice and CALR mutant/EZH2-deficient mice. Both developed ET, but did not develop myelofibrosis or leukemia, and their survival time was equivalent to that of wild type mice.
Next, We performed competitive transplantation with CALR mutant LSKs or CALR mutant/EZH2-deficient LSKs. Although none of them developed ET, we observed increased percentage of donor-derived cells the mice transplanted with CALR mutant LSK or CALR mutant/EZH2-deficient LSK. No difference in chimerism was observed between CALR mutant/EZH2-deficient LSK transplanted mice and CALR mutant LSK transplanted mice. We found that EZH2 deficiency for CALR mutations does not affect progression to MF or the differentiation potential of stem cells.

Free Research Field

血液内科

Academic Significance and Societal Importance of the Research Achievements

本研究により、骨髄増殖性腫瘍ではドライバー遺伝子の種類によってエピゲノム異常の与える影響が異なる事が明らかとなった。この結果により、CALR変異をもつ骨髄増殖性腫瘍の発症や急性転化に寄与するエピゲノム異常を同定し、新規治療薬の開発につながる事が期待できる。また、骨髄増殖性腫瘍患者のドライバー遺伝子やエピゲノム遺伝子変異の種類により予後の層別化を行い、新たな治療戦略の開発につながる事が期待される。