K562 chronic myeloid leukemia cells modify osteogenic differentiation and gene expression of bone marrow stromal cells

被引:0
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作者
Atul Kumar
Trishna Anand
Jina Bhattacharyya
Amit Sharma
Bithiah Grace Jaganathan
机构
[1] Indian Institute of Technology Guwahati,Stem Cell and Cancer Biology Group, Department of Biosciences and Bioengineering
[2] Gauhati Medical College,Department of Hematology
关键词
Bone marrow stroma; Osteoblasts; Therapy resistance; IL6, NFκB signaling; Paracrine factors; Cell-cell communication;
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摘要
Bone marrow (BM) microenvironment plays an important role in normal and malignant hematopoiesis. As a consequence of interaction with the leukemic cells, the stromal cells of the bone marrow become deregulated in their normal function and gene expression. In our study, we found that mesenchymal stem cells (MSC) from BM of chronic myeloid leukemia (CML) patients have defective osteogenic differentiation and on interaction with K562 CML cells, the normal MSC showed reduced osteogenic differentiation. On interaction with K562 cells or its secreted factors, MSC acquired phenotypic abnormalities and secreted high levels of IL6 through NFκB activation. The MSC derived secreted factors provided a survival advantage to CML cells from imatinib induced apoptosis. Thus, a therapy targeting stromal cells in addition to leukemia cells might be more effective in eliminating CML cells.
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页码:441 / 450
页数:9
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