Megakaryocyte, Erythroid and Granulocyte-Macrophage Colony Formation in Myelodysplastic Syndromes

Abstract

Bone marrow progenitor cell assays of three cell lineages, i.e., colony-forming unit megakaryocytes (CFU-Meg), burst-forming unit erythrocytes (BFU-E) and colony-forming unit granulocyte-macrophages (CFU-GM), were performed for 21 patients with myelodysplastic syndromes (MDS). Markedly reduced or absent colony formation was found in 67% of the patients for CFU-Meg and all patients except 2 with refractory anemia (RA) for BFU-E. Abnormal CFU-GM colony formation was found in only 5 of 12 patients with RA and RA with ring sideroblasts, in contrast to all of the RA patients with excess of blasts and excess of blasts in transformation. Defective colony formation of all three cell lineages was seen in 63% of the MDS patients. The colony number of CFU-Meg correlated significantly with the numbers of both BFU-E and CFU-GM. These findings indicate that hematopoiesis in MDS patients is disturbed due to a qualitative or quantitative defect at the multipotent stem cell level.

Measurement of secondary colony formation after 5 weeks in long-term cultures in patients with myelodysplastic syndrome

“…Most reports, using short-term colony cultures, have shown that there is no correlation between the colony growth and the specific bone marrow karyotypes except for 5q− syndrome. 41 Furthermore, our results failed to detect significant differences in secondary CFC numbers between the patients with or without abnormal cytogenetics in the RA + RARS group, while in the RAEB + RAEB-T group such differences were present. This finding suggested that chromosome abnormalities can (at least indirectly) affect secondary CFC numbers in RAEB + RAEB-T, eg during leukemic transformation.…”

“…39 In agreement with our results of LTBMC, there were no clear differences in the colony growth between the FAB subtypes, although patients with RA and RARS generally show normal CFU-GM colony formation. 40,41 However, we demonstrated normal secondary colony formation in only 19.4% (seven of 36) of RA and RARS patients, suggesting that this parameter is more sensitive and perhaps reflects more precisely the defect of hematopoietic stem cell compartment than the conventional culture method. While deficiency in the growth and output of clonogenic cells has been previously shown to be greatly reduced in the majority of MDS bone marrow, no significant abnormalities in the stromal compartment have been demonstrated.…”

Colony-forming unit-megakaryocyte (CFU-meg) numbers and serum thrombopoietin concentrations in thrombocytopenic disorders: an inverse correlation in myelodysplastic syndromes

“…The mean CFUmeg number of healthy controls by this method was three or four times the values obtained previously with the fibrin clot culture system. [17][18][19][20] Although the new system seems better than previous methods of culturing CFU-meg, it only provides Leukemia the number of CFU-meg per BMLD cell for different types of bone marrow cells in different diseases. We need to be cautious when interpreting the data as it does not provide the absolute number of CFU-meg per constant number of BM cells.…”

“…27 Previous studies have demonstrated that CFU-meg numbers in MDS were normal in some patients, but decreased in most. 18,28 In addition, the number of megakaryocytes per colony was also reported to be reduced. 29 Consistent with these studies, two-thirds of the patients, group III in our study, showed reduced numbers of CFU-meg; most of them were small colonies.…”

Enhanced growth of myelodysplastic colonies in hypoxic conditions

“…Although a number of hypotheses based upon the preleukemia paradigm have been explored [24][25][26][27] The absence of a coherent mechanistic explanation for these disorders has prompted us to reexamine the assumptions behind current models of MDS [21][22][23]. The marrow of MDS patients consistently demonstrates decreased hematopoietic progenitor colonies [29][30][31][32][33][34] as well as enhanced levels of apoptosis [35][36][37][38][39][40][41][42][43][44][45][46][47]. These two findings are felt to explain the paradox of a hypercellular bone marrow with profound peripheral cytopenias observed in MDS patients [48] and suggests that a propensity to apoptosis is responsible for the initiation of these disorders.…”