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Acta Pharmacol Sin. 2017 Nov;38(11):1475-1485. doi: 10.1038/aps.2017.116. Epub 2017 Aug 24.

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

Author information

  • 1Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • 2Department of Hematology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
  • 3Department of Hematology, Wuhan Central Hospital, Wuhan 430000, China.
  • 4Department of Hematology, Jinzhou Central Hospital, Jinzhou 434020, China.
  • 5Department of Hematology, Xiangyang Central Hospital, the Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, China.

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.

PMID:
28836580
PMCID:
PMC5672071
[Available on 2018-11-01]
DOI:
10.1038/aps.2017.116
[PubMed - in process]
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