In vitro growth of bone marrow-derived multipotent and lineage-restricted hematopoietic progenitor cells in myelodysplastic syndromes.
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.
Carlo-Stella
C
C
Cazzola
M
M
Bernasconi
P
P
Bergamaschi
G
G
Dezza
L
L
Pedrazzoli
P
P
Rosti
V
V
Tomaselli
S
S
Zappone
E
E
D000753:Anemia, Refractory / Q000473:pathology*; D000754:Anemia, Refractory, with Excess of Blasts / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured; D002999:Clone Cells / Q000473:pathology; D003114:Colony-Forming Units Assay; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans