Identification of leukemia-initiating cells in an inv(3)(q21q26) mouse model

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670463
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Tohoku University
• Principal Investigator: Yamamoto Masayuki 東北大学, 医学(系)研究科(研究院), 教授 (50166823)
• Co-Investigator(Kenkyū-buntansha): SUZUKI MIKIKO 東北大学, 大学院医学系研究科, 講師 (80508309)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 染色体転座 / 染色体逆位 / 白血病 / EVI1 / GATA2

Outline of Final Research Achievements

Chromosomal translocation and inversion between 3q21 and 3q26 gives rise to acute myeloid leukemia with poor diagnosis. Overexpression of EVI1 gene located on 3q26 driven by GATA2 distal hematopoietic enhancer located on 3q21 is a major cause of leukemogenesis. We previously generated a transgenic mouse model (3q21q26 mouse) recapitulating inv(3)(q21q26) allele by linking two bacterial artificial chromosome clones. To identify leukemia-initiating cells in leukemia with inv(3)(q21q26), we analyzed the leukemic 3q21q26 mouse bone marrow cells. The 3q21q26 mice developed leukemia in which B cell marker B220+ and myeloid cell marker Gr1+ populations were expanded. In these leukemic cells, B220+/Gr1-/c-Kit+ cells exhibited blast-like morphology and have colony-forming ability. In addition, nude mice, into which B220+/Gr1-/c-Kit+ cells were transplanted, developed leukemia. These results indicate that B220+/Gr1-/cKit+ cells contained leukemia-initiating cells in the leukemic 3q21q26 mice.

Free Research Field

分子生物学