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- W2109783002 abstract "Disruptions to interactions between cells of stromal and haematopoietic lineages caused by chemotherapy treatment alter steadystate proliferation, differentiation and maintenance of stem cell niches, and are associated with skeletal defects known to develop after intensive chemotherapy treatment. The anti-metabolite dihydrofolate reductase inhibitor Methotrexate (MTX) is used commonly to treat Acute Lymphoblastic Leukemia and some solid tumours, known to cause haematopoietic toxicity and bone loss in cancer patients. However, the cellular/molecular mechanisms associated with MTX damage to the bone and bone marrow are yet to be fully elucidated. In this study, short-term MTX chemotherapy (five oncedaily injections at 0.75 mg/kg/day) was conducted in rats to investigate the damage to and subsequent recovery of the bone marrow microenvironment and the potential role of the CXCL12/ CXCR4 axis. Marrow cell density 6, 9 and 10 days after the initial MTX dose was significantly reduced, which was accompanied by an increase in marrow adipocyte number, although both returned to normal by day 14. Consistent with the reduced cellularity, MTX caused a reduction in marrow cell proliferation on days 6 and 9 as measured by BrdU labelling. In addition, a CFU-GM assay of isolated marrow cells was used to estimate contents of committed granulocyte-macrophage progenitor cells, which revealed a reduction in colonies on day 6 but recovery on day 9. Consistent with the increase in adipocyte number, there was an increase in adipocyte formation in an ex vivo assay of isolated bone marrow stromal cells and an increase in adipogenic differentiation regulator PPAR-g expression in bone. To investigate the effects of MTX on marrow stromal progenitor numbers, a CFU-F assay plus Alkaline Phosphatase staining was performed, which revealed a significant decrease in positive colonies on days 6 and 9 returning to near normal by day 14. This study illustrates that acute MTX chemotherapy transiently depletes the bone marrow of its steady-state haematopoietic and stromal progenitors, reducing haematopoietic cellularity and osteogenesis and increasing marrow fat content, which have the capacity to recover by day 14 subsequent to damage." @default.
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- W2109783002 date "2009-05-01" @default.
- W2109783002 modified "2023-09-26" @default.
- W2109783002 title "Damage and recovery of bone marrow microenvironment after acute Methotrexate chemotherapy" @default.
- W2109783002 doi "https://doi.org/10.1016/j.bone.2009.01.381" @default.
- W2109783002 hasPublicationYear "2009" @default.
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