@article{APS9677,
author = {Fen-fen FU and Xiao-jian ZHU and Hong-xiang WANG and Li-ming ZHANG and Guo-lin YUAN and Zhi-chao CHEN and Qiu-bai LI},
title = {BCR-ABL1-positive microvesicles malignantly transform human bone marrow mesenchymal stem cells in vitro },
journal = {Acta Pharmacologica Sinica},
volume = {38},
number = {11},
year = {2017},
keywords = {},
abstract = {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.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9677}
}