Identification of galectin-1 as a novel mediator for chemoresistance in chronic myeloid leukemia cells

• Published in: Oncotarget Vol. 7; no. 18; pp. 26709 - 26723
• Main Authors: Luo, Wu, Song, Li, Chen, Xi-Lei, Zeng, Xiang-Feng, Wu, Jian-Zhang, Zhu, Cai-Rong, Huang, Tao, Tan, Xiang-Peng, Lin, Xiao-Mian, Yang, Qi, Wang, Ji-Zhong, Li, Xiao-Kun, Wu, Xiao-Ping
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 03.05.2016
• Subjects: ATP Binding Cassette Transporter, Sub-Family B - metabolism; Drug Resistance, Neoplasm - physiology; Galectin 1 - metabolism; Gene Expression Regulation, Neoplastic - physiology; Humans; K562 Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Proteomics; Research Paper; P38 MAPK; chronic myelogenous leukemia; MDR1; chemoresistance; galectin-1
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.8489

Multidrug resistance protein-1 (MDR1) has been proven to be associated with the development of chemoresistance to imatinib (Glivec, STI571) which displays high efficacy in treatment of BCR-ABL-positive chronic myelogenous leukemia (CML). However, the possible mechanisms of MDR1 modulation in the process of the resistance development remain to be defined. Herein, galectin-1 was identified as a candidate modulator of MDR1 by proteomic analysis of a model system of leukemia cell lines with a gradual increase of MDR1 expression and drug resistance. Coincidently, alteration of galectin-1 expression triggers the change of MDR1 expression as well as the resistance to the cytotoxic drugs, suggesting that augment of MDR1 expression engages in galectin-1-mediated chemoresistance. Moreover, we provided the first data showing that NF-κB translocation induced by P38 MAPK activation was responsible for the modulation effect of galectin-1 on MDR1 in the chronic myelogenous leukemia cells. Galectin-1 might be considered as a novel target for combined modality therapy for enhancing the efficacy of CML treatment with imatinib.