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


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-?1. These BM-MSCs in turn could trigger the TGF-?1-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-?1 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.

SUBMITTER: Fu FF 

PROVIDER: S-EPMC5672071 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Fu Fen-Fen FF   Zhu Xiao-Jian XJ   Wang Hong-Xiang HX   Zhang Li-Ming LM   Yuan Guo-Lin GL   Chen Zhi-Chao ZC   Li Qiu-Bai QB  

Acta pharmacologica Sinica 20170824 11


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  ...[more]

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