SENSITIVITY OF HEMATOPOIETIC PROGENITORS OF ACUTE MYELOBLASTIC-LEUKEMIA TO NEW COMPOUNDS DERIVED FROM MARINE ORGANISMS

Results of chemotherapy in acute myeloid leukemia (AML) have improved slowly or not at all in the last decade. We evaluated the effect of Ei latin and Norsegoline, two new aromatic alkaloids derived from the Red Sea purple tunicate Eudistoma sp., on in vitro proliferation and diff erentiation of leukemic cell lines and blast cells of three AML patien ts. These biological properties were studied in two complementary cult ure methods. The first is a clonogenic assay that supports colony form ation in agar and reflects terminal divisions. The second is a suspens ion assay where clonogenic cells increase exponentially and reflects s elf-renewal. Eilatin and Norsegoline, at micromolar concentrations, su ppressed, in a dose-dependent manner, both primary colony formation in agar and the recovery of clonogenic cells from suspension culture in the investigated cell lines and in fresh blasts. Furthermore, both alk aloids were more effective in inhibiting clonogenic cells grown in sus pension than primary colonies grown in agar. In addition, these agents were able to induce immunophenotypic maturation of leukemic cell line s (upregulation of CD14 and CD11 and down-regulation of CD34 antigens) . Our results indicate that Eilatin and Norsegoline significantly inhi bit self-renewal capacity of leukemic progenitors and may provide a us eful new tool for the treatment of AML patients.