Establishment of a platform for elucidation of molecular pathogenesis of leukemia and antileukemia therapy based on integrated pathway analysis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24249055
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: KUROKAWA MINEO 東京大学, 医学部附属病院, 教授 (80312320)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: Refractory leukemia / Signaling pathway / EVI-1 / BAALC / DNMT3A / NF-kB / JAK2V617F

Outline of Final Research Achievements

In this study, we elucidated the down-stream pathway and specific therapeutic target of molecules associated with poor prognosis in acute myeloid leukemia, such as Evi-1 and BAALC, as well as a collaborative factor for Evi-1 induced leukemogenesis and a maintenance mechanism of resistant leukemia initiating cells. By using Evi-1-IRES-GFP knock-in mice, we also showed that Evi-1 marks leukemia initiating cells and Evi-1 is associated with chemoresistance in chronic myeloid leukemia. In addition, we revealed pathogenesis of myeloid malignancies in an integrated manner by demonstrating a mechanisms of leukemia progression, interaction between leukemia cells and surrounding cells and an essential role epigenetic abnormalities play in leukemogenesis. These results provide a foundation to develop novel molecular targeted therapies for refractory hematological malignancies.

Free Research Field

血液内科学