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  • Title: In vitro growth of bone marrow-derived multipotent and lineage-restricted hematopoietic progenitor cells in myelodysplastic syndromes.
    Author: Carlo-Stella C, Cazzola M, Bernasconi P, Bergamaschi G, Dezza L, Pedrazzoli P, Rosti V, Tomaselli S, Zappone E.
    Journal: Haematologica; 1989; 74(2):181-6. PubMed ID: 2501171.
    Abstract:
    The aim of the present study was to evaluate the incidence of bone marrow-derived multipotent (CFU-GEMM), megakaryocytic (CFU-Mk), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells in 22 patients with myelodysplastic syndromes (MDS), and to investigate the role of hematopoietic accessory cells (T-lymphocytes and monocytes) as a possible cause of growth derangement. As compared to normal controls (n = 15), growth values in the 22 patients (mean +/- SEM) were significantly reduced for CFU-GEMM (0.4 +/- 0.1 versus 7 +/- 1, P less than 0.0005), CFU-Mk (1.4 +/- 0.5 versus 18 +/- 4, P less than 0.0005), BFU-E (2.2 +/- versus 40 +/- 6, P less than 0.0005), and CFU-GM (19 +/- 5 versus 65 +/- 10, P less than 0.0005). The growth of CFU-GEMM was abnormal at an early stage in the clinical development of MDS, sometimes even when CFU-GM formation was still normal. Colony-formation was unaffected by removal of hematopoietic accessory cells. Although no correlation was found between the incidence of lineage-restricted progenitors and the degree of peripheral cytopenia, derangement of colony growth was more pronounced in patients with worse prognosis. We conclude that: (i) the grossly defective CFU-GEMM growth supports the concept of MDS as clonal disorders of hematopoietic multipotent stem cells; (ii) a progressive impairment of in vitro hematopoiesis occurs in association with the clinical progression of the myelodysplastic syndromes.
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