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Abstract :
[fr] It is suspected that bone marrow (BM) microenvironmental factors may influence the evolution of chronic myeloid leukemia (CML). For this study, we postulated that adipocytes and lipids could be involved. To test this hypothesis we realized co-cultures of adipocytes and two BCR-ABL positive cell lines (PCMDS and K562) using T cell (Jurkat) and stroma cell (HS-5) lines as controls. We also treated leukemic cell lines with 50 to 250 µM of stearic, oleic, linoleic or alpha-linolenic acids with and without leptin. Survival, proliferation, leptin production, OB-R isoforms (OB-Ra and OB-Rb), phosphoinositide 3-kinase (PI3k) and BCL-2 expression were tested after 24h, 48h and 72h. In vitro, adipocytes induced a decrease in chronic myeloid leukemic cell (CML) proliferation and an increase in lipid accumulation in leukemic cells. On the one hand, CML cell lines induced adipocytes but not HS-5 cell death. Chromatography analysis showed that cells of BM microenvironment were full of saturated (SFA) and monounsaturated (MUFA) fatty acids, fatty acids that protect tumor cells against external agents. Stearic acid increased the expression of Bcl-2, whereas oleic and linoleic acids had no effects. In contrast, alpha-linolenic acid decreased the proliferation and the survival of CML cell lines; it also decreased BCL-2 and OB-R expression in these cell lines. The effect of alpha-linolenic acids seemed to be related to PI3K pathway and Bcl-2 inhibition. Leptin production (344.68±59.7 pg/ml) was also detected in the co-culture medium. Leptin alone had no effect. But in the presence of leptin, the effect of alpha-linolenic acid on proliferation, survival, OB-R and BCl-2 was reduced.
