Kumar Atul, Anand Trishna, Bhattacharyya Jina, Sharma Amit, Jaganathan Bithiah Grace
Stem Cell and Cancer Biology Group, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India.
Department of Hematology, Gauhati Medical College, Guwahati, Assam, India.
J Cell Commun Signal. 2018 Jun;12(2):441-450. doi: 10.1007/s12079-017-0412-8. Epub 2017 Sep 30.
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.
骨髓(BM)微环境在正常和恶性造血过程中发挥着重要作用。由于与白血病细胞相互作用,骨髓基质细胞的正常功能和基因表达出现失调。在我们的研究中,我们发现慢性髓性白血病(CML)患者骨髓中的间充质干细胞(MSC)具有成骨分化缺陷,并且在与K562 CML细胞相互作用时,正常的MSC成骨分化能力降低。在与K562细胞或其分泌因子相互作用时,MSC出现表型异常并通过NFκB激活分泌高水平的IL6。MSC衍生的分泌因子为CML细胞提供了对伊马替尼诱导的凋亡的生存优势。因此,除白血病细胞外,靶向基质细胞的疗法可能在消除CML细胞方面更有效。