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Anti-leukemic therapies induce cytogenetic changes of human bone marrow-derived mesenchymal stem cells

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Abstract

Both bone marrow hematopoietic cells (BM-HCs) and mesenchymal stem cells (BM-MSCs) may have cytogenetic aberrations in leukemic patients, and anti-leukemic therapy may induce cytogenetic remission of BM-HCs. The impact of anti-leukemic therapy on BM-MSCs remains unknown. Cytogenetic studies of BM-MSCs from 15 leukemic patients with documented cytogenetic abnormalities of BM-HCs were investigated. To see the influence of anti-leukemic therapy on BM-MSCs, cytogenetic studies were carried out in seven of them after the completion of anti-leukemic therapy, including anthracycline/Ara-C-based chemotherapy in two patients, high-dose busulfan/cyclophosphamide-based allogeneic transplantation in two patients, and total body irradiation (TBI)-based allogeneic transplantation in three patients. To simulate the effect of TBI in vitro, three BM-MSCs from one leukemic patient and two normal adults were irradiated using the same dosage and dosing schedule of TBI and cytogenetics were re-examined after irradiation. At the diagnosis of leukemia, two BM-MSCs had cytogenetic aberration, which were completely different to their BM-HCs counterpart. After the completion of anti-leukemic therapy, cytogenetic aberration was no longer detectable in one patient. Unexpectedly, BM-MSCs from three patients receiving TBI-based allogeneic transplantation acquired new, clonal cytogenetic abnormalities after transplantation. Similarly, complex cytogenetic abnormalities were found in all the three BM-MSCs exposed to in vitro irradiation. In conclusion, anti-leukemic treatments induce not only “cytogenetic remission” but also new cytogenetic abnormalities of BM-MSCs. TBI especially exerts detrimental effect on the chromosomal integrity of BM-MSCs and highlights the equal importance of investigating long-term adverse effect of anti-leukemic therapy on BM-MSCs as opposed to beneficial effect on BM-HCs.

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Acknowledgement

This work was supported in part by the research grant from Taiwan National Science Council (NSC-96-3111-B-039-001), Department of Health, China Medical University Hospital Cancer Research of Excellence (DOH-100-TD-C-111-005), and China Medical University Hospital (DMR-95-036) All the authors report no conflicts of interest.

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Authors and Affiliations

  1. Stem Cell Research Lab., Department of Medical Research, China Medical University Hospital, 2 Yuh Der Road, Taichung, 404, Taiwan

    Su-Peng Yeh, Wen-Jyi Lo & Chiao-Lin Lin

  2. Division of Hematology and Oncology, Department of Medicine, China Medical University Hospital, 2 Yuh Der Road, Taichung, 404, Taiwan

    Su-Peng Yeh, Yu-Min Liao, Chen-Yuan Lin, Li-Yuan Bai & Chang-Fang Chiu

  3. Department of Radiation Oncology, China Medical University Hospital, 2 Yuh Der Road, Taichung, 404, Taiwan

    Ji-An Liang

  4. China Medical University, 2 Yuh Der Road, Taichung, 404, Taiwan

    Su-Peng Yeh, Ji-An Liang & Chang-Fang Chiu

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  1. Su-Peng Yeh
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Correspondence to Chang-Fang Chiu.

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Yeh, SP., Lo, WJ., Lin, CL. et al. Anti-leukemic therapies induce cytogenetic changes of human bone marrow-derived mesenchymal stem cells. Ann Hematol 91, 163–172 (2012). https://doi.org/10.1007/s00277-011-1254-8

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  • DOI: https://doi.org/10.1007/s00277-011-1254-8

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