Differentiation in acute myeloid leukemia and myelodysplastic disorders. Is differentiation-induction therapy...

In this review we have discussed the data which indicates that differentiation can indeed occur to a limited degree in the neoplastic cells in acute leukemia and myelodysplastic syndromes. Attempts to increase the degree of differentiation as an approach to the treatment of these disorders have utilised a variety of chemical agents which have been reported to exert such an effect in vitro. Analysis of the results, however, indicates that beneficial effects of these agents in patients is due to cytotoxic action which selectively reduces the neoplastic cell population. Leukemic cells can also undergo incomplete differentiation in vitro when exposed to appropriate growth factors, which raises the question of whether leukemia and myelodysplasia can be treated by the induction of differentiation in the malignant cells following the administration of these agents. This question, and questions about the nature of complete remission, will be answered in the coming years by clinical trials of growth factors, and further studies of the DNA in mature cells to analyse whether these cells are derived from leukemic progenitors.