Marrow cytogenetic and cell-culture analyses of the myelodysplastic syndromes: insights to pathophysiology and prognosis.

Abstract

Marrow cytogenetic and granulocyte-macrophage colony formation (CFU-GM) studies were performed on 34 previously untreated patients with documented myelodysplastic syndromes seen between January 1978 and June 1982. All patients were managed without chemotherapy until progression to acute leukemia was observed. All 10 patients with exclusively abnormal marrow metaphases developed acute leukemia (100%) while only one (7%) of 14 patients with solely normal marrow metaphases subsequently developed leukemia (p less than 0.001). Three (42%) of the seven patients with both normal and abnormal marrow metaphases developed acute leukemia. Fifteen (86%) of the 19 patients with either large cluster or no growth patterns developed acute leukemia while only two (13%) of 15 patients with either small cluster or colony forming growth patterns developed acute leukemia (p less than 0.001). Abnormal marrow cytogenetic status correlated with abnormal marrow CFU-GM growth pattern (p less than 0.05). Analysis of CFU-GM sensitivity to inhibition by prostaglandin E was performed in 12 patients. Nine patients showed CFU-GM refractoriness to inhibition by prostaglandin E. Seven of these patients eventually developed leukemia. Three patients had CFU-GMs which were initially sensitive to prostaglandin E inhibition. In these three patients, a loss of CFU-GM sensitivity to prostaglandin E was observed prior to their progression to morphologically identifiable acute leukemia.

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

“…Three reports pointed out a correlation between colony formation and specific chro mosome abnormalities [8,9,25], while two other reports did not find any relationship between these two param eters [13,26]. Our present study did not reveal any correla tion between colony formation by the three cell lines and the abnormal karyotype.…”

Trisomy 14 is a non‐random karyotypic abnormality associated with myeloid malignancies

“…The most common trisomies reported in myeloid neoplasia are 8, 9, 12 and 21 (Heim & Mitelman, 1986). Of these, only trisomy 21 is associated with myeloid malignancy both as a congenital (Krivit & Good, 1957;Miller et al, 1961;Lin et al, 1980;Lazarus et al, 1981;Morgan et al, 1985;Hayashi et al, 1988) or acquired (Heim & Mitelman, 1986;Knapp et al, 1985;Gold et al, 1983) abnormality. The most simplistic hypothesis relating neoplasm and trisomy would be a dosage effect relating to the presence of a higher copy number of genes potentially relevant to proliferation (Heim & Mitelman, 1986).…”

Bone Marrow Cultures in Dysmyelopoietic Syndrome: Diagnostic and Prognostic Evaluation

“…The results of the statistical analysis (Stu dent's t test) were highly significant for the means of CFU-C (p< 0.001) and not significant for the means of BFU-E. Quantitation of CFU-C (11 or less) was a significant parameter to determine the development of acute leukemia. A recent publication by Golde et al [10] showed a significant correlation between the growth pattern of in vitro bone marrow cultures and the progression to AML, in addition to the other pa rameters involved such as chromosomal abnormali ties and sensitivity to the inhibitory effect of prostag landin E on CFU-GM growth.…”