Circumventing resistance at bone marrow microenvironment in acute myeloid leukemia

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461412
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kobe University
• Principal Investigator: Minami Yosuke 神戸大学, 医学部附属病院, 講師 (60513752)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 白血病 / 分子標的療法 / ヘッジホッグシグナル

Outline of Final Research Achievements

Smoothened (SMO) regulates the Hedgehog (Hh) pathway. Gene set enrichment analysis (GSEA) revealed that SMO inhibitor treatment induced effects on the self-renewal signatures and the cell-cycling regulations associated with leukemic stem cells (LSCs)-like properties. I examined the pluripotency factor, NANOG expression in bone marrow cells, based on the previous report that downstream effectors in the Hh pathway, GLI directly binds to the NANOG promoter and that the GLI- NANOG axis promotes stemness and growth in several cancers. Change of NANOG transcripts was closely associated with the GLI-target genes. Furthermore, by backing to the pre-clinical experimental systems, NANOG transcript level decreased during SMO inhibitor treatment. GSEA revealed that treatment with SMO inhibitor modulates self-renewal and cell-cycling signatures in AML. NANOG transcript can be a responsive biomarker during the therapy.

Free Research Field

白血病分子標的療法