Retinoids are a group of naturally-occurring and synthetically produced analogs of vitamin A. We have found previously that retinoids stimulate normal human myelopoiesis and erythropoiesis in vitro and inhibit leukemic blast cell clonal proliferation in vitro. We shall confirm our initial experiments that retinoids inhibit leukemia cell clonal growth. Also, we shall use leukemia cells from patients and cell lines to investigate if leukemic blast cells have cytoplasmic retinoic acid binding proteins (cRABP) and correlate the presence of cRABP in blast cells with an observable cytotoxic effect of retinoid in vitro. Chemotherapy is the current treatment of human myeloid leukemia, but these agents do not prolong remission nor are they effective in relapse. Initially, we will test the antileukemic potential of 13-cis retinoic acid on a myeloid leukemia rat model using various dose schedules of the retinoids and combining retinoids with various known chemotherapeutic agents. Subsequently, we shall treat myeloid leukemia patients in remission with 13-cis retinoic acid to attempt to prolong remission and to prolong survival. Likewise, preleukemia patients especially, whose neoplastic clone is marked by a chromosomal abnormality, will receive 13-cis retinoic acid and the effect of the retinoid on the normal and abnormal hematopoietic clone of the patients will be monitored. The cytotoxic effect of 13-cis retinoic acid on the growth of the preleukemia and leukemia colony forming cells in vitro will be correlated with the clinical efficacy of 13-cis retinoic acid in the patients with preleukemia and acute myelogenous leukemia in remission.
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