2013 Fiscal Year Final Research Report

Establishment of new targeted therapy against acute blastic transformation of chronic myeloid leukemia

Research Project

Project/Area Number	24790962
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Hematology
Research Institution	The University of Tokyo
Principal Investigator	TOMOHIKO Sato 東京大学, 医学部附属病院, 助教 (90553694)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	白血病幹細胞
Research Abstract	Introduction of CML into Evi1-IRES-GFP knock-in mice, a versatile HSC-reporter strain, enables us to separate Evi1-high CML cells from the individual. Evi1-IRES-GFP allele models of CML in chronic phase (CML-CP) revealed that Evi1 is predominantly enriched in the stem cell fraction and associated with an enhanced proliferative as well as a leukemia-initiating capacity and that Evi1-high CML-CP cells exhibit resistance to TKIs. Overexpressing BCR-ABL and NUP98-HOXA9 in Evi1-IRES-GFP knock-in mice to model CML in blast crisis (CML-BC), in which Evi1-high cells turned to be a major population as opposed to a minor population in CML-CP models, showed that Evi1-high CML-BC cells have a greater potential to recapitulate the disease and appear resistant to TKIs. Given that Evi1 heterozygosity ameliorates CML-CP and CML-BC development and that the combination of Evi1 and BCR-ABL causes acute myeloid leukemia resembling CML-BC, Evi1 could regulate CML development as a potent driver.