functional roles of CAMK2G in myelofibrosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20827
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Sasaki Ken 東京大学, 医学部附属病院, 特任臨床医 (10907702)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 骨髄線維症

Outline of Final Research Achievements

Myelofibrosis (MF) is a myeloproliferative neoplasm which is associated with bone marrow fibrosis and extramedullary hematopoiesis, followed by progressive hematopoietic failure and leukemic transformation. Although JAK1/2 inhibition is effective to alleviate symptoms of MF, it does not result in eradicating MPN clones, and the inhibitor-resistant clones emerge during the treatment. To overcome this problem, we need to develop a new therapeutic strategy.
The previous study revealed CAMK2G inhibition significantly prolonged the survival of MF model mice and ameliorated splenomegaly. CAMK2G inhibition is effective in the JAK2 inhibitor-resistant cells.
In this study, we will confirmed the effectiveness of CAMK2G inhibition with CAMK2G knockout mice. By using these mice we can perform transcriptome analyses including RNA seq to identify the signaling pathways related to CAMK2G, and these results can lead to the development of new strategies of new treatments of MF.

Free Research Field

血液内科

Academic Significance and Societal Importance of the Research Achievements

本研究ではCAMK2Gノックアウトマウスを用いて、骨髄線維症におけるCAMK2Gの意義と治療標的としての可能性について検証を行った。骨髄線維症の治療には経口JAK2阻害剤が臨床において使用されている。症状改善効果を示すが、腫瘍細胞を排除はできないため治療効果限定的で予後不良である。また、長期投与による耐性化があり完治は見込めないことや、骨髄抑制などの副作用も問題となる。現在さまざまな方法で治療標的の同定、解析が行われているが、新規治療薬の開発は進んでおらず、本研究は新規治療薬開発において意義のある研究であると考えられる。