The role of mutant Calreticulin and HMGA2 in myeloproliferative neoplasms

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09483
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Fukushima Medical University
• Principal Investigator: Ogawa Kazuei 福島県立医科大学, 医学部, 教授 (40423800)
• Co-Investigator(Kenkyū-buntansha): 植田 航希 福島県立医科大学, 医学部, 助教 (80632190) ; 池田 和彦 福島県立医科大学, 医学部, 准教授 (90381392)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: MPN / CALR

Outline of Final Research Achievements

Myeloproliferative neoplasms (MPNs) are a group of diseases in which mature hematopoietic cells proliferate. Recently, insertion/deletion mutations in exon 9 of Calreticulin (CALR) were discovered in MPNs. However, the role of the mutant CALR in MPN hematopoiesis are largely unknown. Thus, we generated 2 types of mice with mutant Calr; type 1-like 10 bp deletion (CR10d) and type 2-like 2 bp insertion (CR2i) using genetic modification by CRISPER/Cas9 method. Both mice mimicked mutations in patients with MPN. CR2i mice showed increased spleen weight per body weight and a reduced bone marrow T cell ratio compared with wild-type mice. Both CR10d and CR2i mice showed increased bone marrow myeloid cells. We are studying the effect of the Calr mutants on hematopoietic stem cell and progenitor function by BM transplant experiments and progenitor assays. In addition, we will generate Hmga2+CR10d and Hmga2+CR2i mice by crossing Hmga2-transgenic mice and mice with mutant Calr.

Free Research Field

血液学