Establishment of in vitro model for essential thrombocythemia by mutant calreticulin

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19587
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Juntendo University
• Principal Investigator: MIZUKAMI Yoshihisa 順天堂大学, 医学(系)研究科(研究院), 博士研究員 (30756698)
• Research Collaborator: Komatsu Norio 順天堂大学, 医学部, 血液学講座 (50186798) ; Araki Marito 順天堂大学, 医学部 輸血・幹細胞制御学, 准教授 (80613843)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 骨髄増殖性腫瘍 / calreticulin / JAK2 / ドライバー変異 / 骨髄線維症 / 本態性血小板血症 / iPS細胞 / 造血幹細胞

Outline of Final Research Achievements

Somatic mutations in the calreticulin (CALR) gene have been found in most patients with myeloproliferative neoplasms (MPNs). Mutant CALR activates the thrombopoietin receptor, which promote the development of MPNs. However, the roles of mutant CALR in human hematopoietic cell differentiation remain unknown. To examine the effect of mutant CALR on hematopoietic cell differentiation, we generated induced pluripotent stem cells from an essential thrombocythaemia (ET) patient with CALR mutation. Megakaryopoiesis was observed in hematopoietic progenitor cells with mutant CALR rather than in healthy ones, suggesting that the system recapitulates megakaryocytosis occurred in the bone marrow of CALR-mutant ET patients. We established an in vitro model system that recapitulates megakaryopoiesis caused by mutant CALR. This system can be used to validate therapeutic compounds for MPN patients with CALR mutations and in detailed studies on mutant CALR in human hematological cell differentiation.

Free Research Field

血液学