Utilizing in vitro culture techniques we propose to study human granulopoietic control mechanisms with major focus being directed toward an understanding of the changes which occur in malignant diseases of the granulopoietic system--acute myeloid leukemia and evolving myeloproliferative disorders. In specific terms we plan to test an hypothesis regarding multiclonal populations in acute leukemia marrow, and study leukemic clones directly for understanding their proliferative characteristics, responsiveness to humoral stimulatory and inhibitory substances, sensitivity to drug therapy, impact on adjacent normal granulocytic clones, and for detecting small numbers of residual leukemic precursor cells. The recent development of techniques permitting the proliferation of granulocytic clones from human granulocyte progenitor cells in agar and liquid culture, and methods for effectively separating these disparate cell populations by their density distribution patterns allows these studies, and studies evaluating colony stimulating factor (CSF) levels, to be performed. Clinical correlates will be provided by basing our studies on patient populations being manged according to prospective protocols. To date the results suggest that clinical benefits may be derived from our studies by anticipating leukemic relapse or evolution, and for devising chemotherapeutic regimens with diminished potential for neutropenic toxicity. Our studies should enable us to evaluate critical factors involved in the transition from relatively benign to frankly malignant disease states. Parallel studies will be performed in the nonmalignant disorders of granulopoiesis for purposes of comparison and understanding pathogenetic mechanisms underlying these disorders. BIBLIOGRAPHIC REFERENCES: Embury, S.H., Elias, L., Heller, P.H., Hood, C.E., Greenberg, P.L., Schrier, S.L.: Remission maintenance therapy in acute myelogenous leukemia. West, J. Med., April, 1977. Embury, S.H., Elias, L., Heller, P.H., Hood, C.E., Greenberg, P.L., Schrier, S.L.: Remission maintenance therapy in acute myelogenous leukemia. Clinical Research 25:154a, 1977. (Presented at AFCR meeting, Carmel, February 1977). (Abstract).