The mechanism of autocrine and paracrine growth promotion of CML cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860792
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: SUGITANI Mio 京都府立医科大学, 医学部附属病院, 研究員 (60648749)
• Co-Investigator(Kenkyū-buntansha): TANIWAKI Masafumi 京都府立医科大学, 医学部附属病院, 教授 (80163640) ; KURODA Junya 京都府立医科大学, 医学部附属病院, 講師 (70433258)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 慢性骨髄性白血病 / Galectin-3 / 骨髄腫瘍環境由来治療抵抗性 / オートクライン・パラクライン / 幹細胞能

Outline of Final Research Achievements

Tyrosin kinase inhibitors(TKIs) for BCR-ABL have dramatically improved the outcome of chronic myelogenous leukemia(CML). However, the complete elimination of CML clones has been rarely achieved by TKIs due to a variety of protective mechanisms. One reason for TKI resistance is the bone marrow microenvironment(BMME)-mediated drug resistance. We found that BMME-induced galectin-3(Gal-3) in CML plays an important role in drug resistance in previous study. Furthermore, we in this study disclosed the results as follows. ①The bovine SERPINA1-fetal bovine serum albumin complex was specifically suppressed in conditioned medium from Gal-3-overexpressing cells. Suppression of SERPINA1-albumin complex by Gal-3 overexpression led to paracrine growth promotion of CML cells. ②The combination of TKI and PP2A activator FTY720 could overcome Gal-3-mediated drug resistance to TKI. ③ALDH1 known as the marker of cancer stem cell and drug resistance was induced by Gal-3 overexpression in CML cells.

Free Research Field

慢性骨髄性白血病の骨髄腫瘍環境由来治療抵抗性