Acute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis and remarkable resistance to chemotherapeutic agents. Understanding resistance mechanisms against currently available drugs helps to recognize the therapeutic obstacles. Various mechanisms of resistance to chemotherapy or targeted inhibitors have been described for AML cells, including a role for the bone marrow niche in both the initiation and persistence of the disease, and in drug resistance of the leukemic stem cell (LSC) population. The BM niche supports LSC survival through direct and indirect interactions among the stromal cells, hematopoietic stem/progenitor cells, and leukemic cells. Additionally, the BM niche mediates changes in metabolic and signal pathway activation due to the acquisition of new mutations or selection and expansion of a minor clone. This review briefly discusses the role of the BM microenvironment and metabolic pathways in resistance to therapy, as discovered through AML clinical studies or cell line and animal models.
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Scan to discover onlineBackground & Objective: Trapped cell population in leukoreduction filters (LRFs) contains such a significant number of CD34 + hematopoietic stem cells that can be recovered to be used in research studies.Methods: Samples (n=20) were obtained from 10 first-time donors and 10 regular blood donors with more than 30 times blood donation. After separating leukocytes from LRFs by backflushing, total leukocyte number and differential count were determined in both groups using an automated haemocytometer. Then cell viability and CD34 + cell quantification were assessed using 7-amino-actinomycin D and fluorescent-labeled monoclonal antibodies using flow cytometry, respectively.Results: Total leukocyte count was 665±164.92×10 6 in the first-time blood donors and 883±233.89×10 6 in the regular donors, which were not significantly different (P=0.08). While the number of CD34 + cells was significantly reduced in the regular donors compared to the first-time donors (0.58±0.20×10 6 /µL vs. 0.36±0.22×10 6 /µL; P=0.034). There was no significant difference in terms of absolute neutrophil count (10.58±3.66×0 6 vs. 13.17±6.45×10 6 /µL; P=0.349), lymphocytes (7.75±3.11×10 6 vs. 10.38±3.77×10 6 /µL; P=0.917), and monocytes (2.31±0.88×10 6 vs. 2.59±1.09×10 6 /µL; P=0.591) between the first-time and regular donor groups, respectively. Based on the correlation coefficients, the participants' age had no significant effect on these variables. Conclusion:The results of this study depicted that regular blood donation reduces the number of CD34 + cells in the peripheral blood (PB) of regular donors while it has no significant effect on the ratio of myeloid to lymphoid cells of the two groups.
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