Development of a novel therapeutic method for myeloproliferative neoplasia by identifying a novel driver mutation and analyzing its function.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16195
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Juntendo University
• Principal Investigator: Imai Misa 順天堂大学, 医学(系)研究科(研究院), 助教 (50709003)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: triple-negative MPN / 骨髄増殖性腫瘍

Outline of Final Research Achievements

Patients with essential thrombocythemia (ET) without typical somatic mutations were classified into those with atypical MPL mutations and those with no mutation. Of these, the latter patients were mostly young women and were at low risk of thrombosis and secondary fibrosis. The blood cells of the patient exhibited polyclonal hematopoiesis, but the stem cells exhibited a capacity to form cell-autonomous megakaryocytic colonies. On the other hand, when Ba/F3 cells was transduced with wild-type MPL and cultured for several weeks in the absence of cytokine, cells gained a capacity to proliferate in the absence of cytokine associated with constitutive activation of MPL downstream molecules. These findings strongly suggested an existence of yet unidentified molecular mechanism for the MPL activation, which may play a role in the development of ET with no mutation.

Free Research Field

血液腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究により、典型的な遺伝子変異の見つからないETの病態の理解を深める知見が得られた。さらに、リガンド非依存性にMPL下流シグナルを活性化する未知のメカニズムが存在することが初めて明らかになるとともに、このメカニズムによりETが発症する可能性が示された。今後の研究により、ET発症の新たな分子基盤が解明されることが見込まれることから、当該患者に対する迅速な診断法や有効な治療法の開発が期待される。