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

作　　者：Fen-fen FU Xiao-jian ZHU Hong-xiang WANG Li-ming ZHANG Guo-lin YUAN Zhi-chao CHEN Qiu-bai LI 

机构地区：[1]Institute of Hematology, Union Hospital, Tongii Medical College, Huazhong University of Science and Technology, Wuhan 430022, China [2]Department of Hematology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China [3]Department of Hematology, Wuhan Central Hospital, Wuhan 430000, China [4]Department of Hematology, Jinzhou Central Hospital, Jinzhou 434020, China [5]Department of Hematology, Xiangyang Central Hospital, the Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, China

出　　处：《Acta Pharmacologica Sinica》2017年第11期1475-1485,共11页中国药理学报（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China to Qiu-bai LI （No 81272624 and 81071943） and to Zhi-chao CHEN （No 81170497）.

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.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.

关 键 词：chronic myeloid leukemia MICROVESICLE bone marrow mesenchymal stem cell BCR-ABL1 TGF-β1 

分 类 号：R[医药卫生]