title: Anti-leukemic therapies induce cytogenetic changes of human bone marrow-derived mesenchymal stem cells.
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.
authors.affiliation: Stem Cell Research Lab., Department of Medical Research, China Medical University Hospital, 2 Yuh Der Road, Taichung, 404, Taiwan.
authors.forename: Su-Peng
authors.initials: SP
authors.lastname: Yeh
authors.forename: Wen-Jyi
authors.initials: WJ
authors.lastname: Lo
authors.forename: Chiao-Lin
authors.initials: CL
authors.lastname: Lin
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Liao
authors.forename: Chen-Yuan
authors.initials: CY
authors.lastname: Lin
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Bai
authors.forename: Ji-An
authors.initials: JA
authors.lastname: Liang
authors.forename: Chang-Fang
authors.initials: CF
authors.lastname: Chiu
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D002869:Chromosome Aberrations / Q000187:drug effects / Q000528:radiation effects; D003582:Cytogenetics / Q000379:methods; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D059785:Karyotype; D007938:Leukemia / Q000628:therapy*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D008875:Middle Aged; D012074:Remission Induction; D014184:Transplantation, Homologous / Q000009:adverse effects*; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents