GROWTH MODULATION AND DIFFERENTIATION OF ACUTE MYELOID-LEUKEMIA CELLSBY JASPAMIDE

We have examined the effect of Jaspamide, a peptide isolated from the marine sponge Hemiastrella minor, on in vitro proliferation and differ entiation of leukemic cell lines and blast cells of three AML patients and compared it to that of cytosine arabinoside (ARA-C). The biologic al properties were studied in two complementary culture methods. The f irst is a clonogenic assay that supports colony formation in agar and reflects terminal divisions. The second is a suspension assay in which clonogenic cells increase exponentially and which reflects self-renew al. Jaspamide, at micromolar concentrations and in a dose-dependent ma nner, suppressed both primary colony formation in agar and the recover y of clonogenic cells from suspension culture in the investigated cell lines and in fresh blasts. Furthermore, Jaspamide was more effective in inhibiting clonogenic cells grown in suspension than primary coloni es grown in agar. In addition, Jaspamide, similarly to ARA-C, was able to induce immunophenotypic maturation of leukemic cell lines (upregul ation of CD14 and CD11 and downregulation of CD34 antigens). Our resul ts indicate that Jaspamide significantly inhibits the self-renewal cap acity of leukemic progenitors and may provide a new useful tool for th e treatment of acute myeloid leukemia (AML) patients.