Identification of a new transcriptional cascade activated by oncogenic JAK2 tyrosine kinase mutant

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K19559
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Juntendo University
• Principal Investigator: EDAHIRO YOKO 順天堂大学, 医学部, 助教 (40732863)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 骨髄増殖性腫瘍 / JAK2V617F

Outline of Final Research Achievements

JAK2V617F, a gain-of-function mutation in the tyrosine kinase JAK2, is frequently detected in myeloproliferative neoplasms (MPN), however its molecular mechanism in terms of MPN development is not fully understood. The identification of the JAK2 mutation in MPN led to the development of JAK2 inhibitors, however, treatment with these inhibitors is associated with side effects caused by blockade of function of wild-type JAK2; therefore, a new therapeutic strategy based on understanding of MPN development is required.
In this study, I found that AP-1 activation by JAK2V617F through c-FOS induction involves an unidentified molecular mechanism suggesting that deregulation of AP-1 plays a role in MPN development. Additionally, the AP-1 reporter assay system I have established should be useful not only for screening novel compounds for MPN treatment but also in studying the novel pathway regulated by JAK2V617F, which would lead to the development of a novel therapeutic strategy against MPN.

Free Research Field

血液内科