Biological and clinical significance of clonogenic assays in patients with myelodysplastic syndromes

Biological and clinical significance of growth pattern of hematopoietic progenitors were investigated in 117 patients with primary myelodysplastic syndromes (MDSs) at referral. Abnormal (i.e., "leukemic" or absent) growth of GM colonies (CFU-GM) and GM clusters was found in 47% of patients with "advanced" MDS (RAEB, RAEB-t, and CMML) and in 15% of "low-risk" (RA/RARS) patients. In vitro erythropoiesis was decreased in most of the patients, with significantly lower number of BFU-E in "advanced" MDS' than in RA/RARS patients. Megakaryocyte progenitors (CFU-MK) were very low or absent in almost all the patients, regardless of the FAB type. Significant correlation was demonstrated between the number of BFU-E and hemoglobin concentration and between number of CFU-MK and platelet count. Growth capacity of GM progenitors appears to be in proportion to "myeloproliferative" capacity of the malignant clone. T-cell depletion had no influence on growth capacity of hematopoietic progenitors, nor did colony growth respond in a dose-dependent manner to different concentrations of LCM. Growth capacity of MDS hematopoietic progenitors was independent of Bournemouth score, of the presence and type of cytogenetic abnormality, and of the expression of CD95 and caspase-3 antigens on bone marrow cells. However, in patients with "abnormal" growth of GM progenitors, CD34 antigen expression was significantly higher than in patients with "normal" growth. "Abnormal" GM growth was found to be independently predictive regarding the survival and the risk for AML development. In contrast, the prognostic value of erythroid and megakaryocyte cultures was found to be limited.