[Role of lipid second messengers involved in the response of leukemic cells to anticancer drugs].
Simple clinical observation suggests that while anti-leukemia agents are efficient at eradicating blasts cells in terminal division, as illustrated, in the case of acute myeloid leukemia, by the high complete remission rate (70%); these agents are relatively inept at eliminating leukemic myeloid progenitors as suggested by the high level of recurrence. This interpretation underlines the apparently natural chemoresistance of cells which compose the myeloid leukemia progenitor compartment. Over the past few years, several studies have shown that similar cellular damage can lead to divers effects such as rapid apoptotic death, differed mitotic death, or a transitory cytostatic effect. Cell response to damage is regulated by a complex and highly regulated network of intracellular signals including cell death signals mediated by ceramide and cell survival signals mediated (at least in part) by diacylglycerol and phosphoinositide-3 phosphates. Cellular fate relies on the balance between these two signaling pathways. This hypothesis opens several prospects on pharmacological manipulation aimed at either favoring cell death or at conferring resistance to anti-cancer agents.
Jaffrézou
J P
JP
E9910 INSERM, Institut Claudius Régaud, Toulouse. jaffrezou@icr.fnclcc.fr
Laurent
G
G
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000633:toxicity; D006801:Humans; D007938:Leukemia / Q000503:physiopathology*; D008055:Lipids / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008055:Lipids; D003630:Daunorubicin