THE BIOCHEMICAL BASIS FOR DEFECTIVE DIFFERENTIATION IN GRANULOCYTIC LEUKEMIA

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The main thrust of this work is to develop biochemical methods for the early diagnosis of granulocytic leukemia and methods for inducing leukemic cells to develop some or all of their functional properties as a means of partially or completely restoring host defense mechanisms in leukemia patients. Work is first aimed at establishing which of the many biochemical steps involved in normal granulocyte differentiation are controlled by humoral regulators. The results will be compared with those obtained from similar studies on leukemic cells at corresponding stages of maturity in order to determine the nature and potential reversibility of the arrested differentiation steps. Biochemical analyses are carried out on mature and immature granulocytes isolated from blood and bone marrow and the effects of external cell regulators on granulocyte differentiation, as measured by changes in the synthesis of specific cellular components, are studied in a defined culture system previously developed in this laboratory. Possible relationships between transforming genes in leukemic myeloblasts and factors involved in the regulation of normal granulocyte differentiation are under investigation.