BCR-ABL1-positive microvesicles malignantly transform human bone marrow mesenchymal stem cells in vitro

• 来源期刊: 中国药理学报（英文版）
• 关键词: chronic myeloid leukemia microvesicle bone marrow mesenchymal stem cell BCR-ABL1 TGF-β1
• 年，卷（期）: 2017,（11）
• 页码范围: 1475-1485
• 页数: 11页
• 语种: 英文
• DOI: 10.1038/aps.2017.116

摘要

The intercellular communication between leukemia cells and bone marrow mesenchymal stem cells (BM-MSCs) plays more important role in chronic myeloid leukemia (CML) than we previously understood.Recently,we found that microvesicles released from human leukemia cell line K562 (K562-MVs) containing BCR-ABL1 mRNA malignantly transformed normal hematopoietic transplants.Here,we investigated whether K562-MVs contribute to the transformation of human bone marrow mesenchymal stem cells (BM-MSCs).We showed that K562-MVs could be integrated into co-cultured normal BM-MSCs and dose-dependently enhanced the proliferation of BM-MSCs.Meanwhile,K562-MVs (400 ng/mL) significantly increased the expression of BCR-ABL1 in these BM-MSCs,accompanied by the enhanced secretion of TGF-β1.These BM-MSCs in turn could trigger the TGF-β1-dependent proliferation of K562 cells.Moreover,we confirmed the presence of BCR-ABL1 in circulating MVs from 11 CML patients.Compared to the normal BM-MSCs,the BM-MSCs from CML patients more effectively increased the BCR-ABL1 expression and TGF-β1 secretion in K562 cells as well as the proliferation of K562 cells.Our findings enrich the mechanisms involved in the interaction between leukemia cells and BM-MSCs and provide novel ways to monitor minimal residual disease and worthwhile approaches to treat CML.