Identification of targetable leukemogenic pathway and leukemic stem cells in MLL fusion-positive leukemia

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461597
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Ehime University
• Principal Investigator: EGUCHI MARIKO 愛媛大学, 医学(系)研究科(研究院), 准教授 (40420781)
• Co-Investigator(Kenkyū-buntansha): Ishii Eiichi 愛媛大学, 大学院医学系研究科, 教授 (20176126) ; Eguchi Minenori 愛媛大学, 医学部附属病院, 講師 (50420782) ; Higashiyama Shigeki 愛媛大学, プロテオサイエンスセンター, 教授 (60202272)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 小児血液学 / 白血病 / 融合遺伝子

Outline of Final Research Achievements

MLL gene rearrangement in infant acute lymphoblastic leukemia and secondary leukemia represent a hallmark of poor prognosis. To obtain necessary information to exploit novel targeting therapy, (1) we examined the cell type that first engraft in the bone marrow and initiate subsequent leukemic cell growth in NOG mice. As a result, the initiating cells expressed gene expression pattern similar to hematopoietic stem cells with abnormal expression of some genes. (2) The role MLL fusion protein on leukemic cell growth and survival was examined in infant ALL samples and in leukemic cell lines. As a result MLL protein suppressed miRNA let-7b and p16 by DNA hypermethylation, whereas it increased the expression of oncogene HMGA2. (3) DNA demethylating reagent 5-azacytidine and HMGA2 inhibitor supressed the growth of leukemic cells with MLL gene rearrangement, which suggested that combination of these reagents may be one of the candidate for targeting therapy toward MLL rearranged leukemia.

Free Research Field

小児科学