Clarification of the pathogenesis of myeloproliferative neoplasms based on the identification of genetic factors in familial cases

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04211
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Juntendo University
• Principal Investigator: Komatsu Norio 順天堂大学, 医学部, 教授 (50186798)
• Co-Investigator(Kenkyū-buntansha): 森下 総司 順天堂大学, 医学部, 助教 (10635866) ; 荒木 真理人 順天堂大学, 医学(系)研究科(研究院), 先任准教授 (80613843)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 骨髄増殖性腫瘍 / iPS細胞 / JAK2V617F変異 / CRISPR/Cas9

Outline of Final Research Achievements

Philadelphia negative myeloproliferative neoplasms (MPN) are clonal disorders characterized by an overproduction of terminally differentiated hematopoietic cells. A majority of patients with MPN harbor JAK2V617F mutation, which is though as a driver gene mutation. Despite of several studies using mouse models and cell lines that link the JAK2V617F mutation and MPN, it was ambiguous whether JAK2V617F mutation alone was sufficient for the presentation of MPN phenotypes such as overproduction of terminally differentiated hematopoietic cells. In this study, we employed iPS cells derived from a healthy donor, introduced JAK2V617F mutation into these iPS cells, and demonstrated that the JAK2V617F alone was sufficient to induce MPN phenotypes in vitro.

Free Research Field

骨髄増殖性腫瘍

Academic Significance and Societal Importance of the Research Achievements

健常人から作ったiPS細胞にJAK2V617F変異を導入したところ、骨髄増殖性腫瘍患者でみられる造血能の亢進を、iPS細胞でも観察することができ、このiPS細胞を用いてJAK2V617F遺伝子の役割を解析することに成功した。このことから、今後はこのiPS細胞を用いて、新たな治療法の開発や病態解明がすすめられることから、その学術的意義、社会的意義は大きいと考える。