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.

Enhancer of Zeste Homolog 2 and Histone Deacetylase 9c Regulate Age-Dependent Mesenchymal Stem Cell Differentiation into Osteoblasts and Adipocytes

“…Primary human MSCs (hMSCs) were isolated from the bone marrow of young and elderly donors with hematologic malignancies (between 12 and 81 years of age) as previously described at China Medical University Hospital by Dr. Su‐Peng Yeh. The Institutional Review Board (IRB) approved the protocols (DMR96‐IRB‐143 and DMR‐IRB‐095), and written informed consent was obtained from patients in all cases at time of enrollment.…”

The oncometabolite R-2-hydroxyglutarate activates NF-κB-dependent tumor-promoting stromal niche for acute myeloid leukemia cells

“…Bone marrow samples were collected from three IDH-mutated AML patients in accordance with the regulations on human trials of Ministry of Health and Welfare, Republic of China. Preparation and culture of bone marrow mesenchymal stem cells from were performed as described previously32. This study was approved by the Institutional Review Board of China Medical University Hospital and signed informed consent was obtained from all patients.…”

Ganoderma spore lipid protects mouse bone marrow mesenchymal stem cells and hematopoiesis from the cytotoxicity of the chemotherapeutic agent

“…Furthermore, transplantation of MSCs could reconstruct the hematopoietic microenvironment and promote the hematopoiesis recovery in mice and patients . Unfortunately, MSCs are frequently destroyed by chemotherapeutic agents in patients, animal models, and cell cultures . The key issue is how to keep MSCs unaffected by the cytotoxicity of chemotherapeutic drugs.…”

“…[4][5][6][7] Unfortunately, MSCs are frequently destroyed by chemotherapeutic agents in patients, animal models, and cell cultures. [8][9][10][12][13][14]25,[29][30][31] The key issue is how to keep MSCs unaffected by the cytotoxicity of chemotherapeutic drugs.…”