Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Blast cell survival in suspension culture is associated with chemoresistance in acute myeloid leukaemia (AML). Autonomous production of IL-1beta by AML blasts is linked with a proliferative response, although its role in survival and hence apoptosis-resistance has not been examined in this disease. Cells that secreted more than 19.7 pg/ml IL-1beta were significantly more resistant to spontaneous apoptosis in 48-h culture than those that produced less than 19.7 pg/ml IL-1beta (P=0.008). Exogenous rhIL-1beta significantly enhanced 48-h survival in 25/29 blast cell samples (P=0.0001). IL-1 receptor ligation is known to activate at least three survival pathways: those mediated by PI-3 kinase, IL-1 receptor-associated kinase (IRAK) and ceramidase. In apoptosis-sensitive AML blasts with a strong survival response to rhIL-1beta, inhibitors of all three pathways down-modulated an IL-1beta-mediated increase in blast survival, but only the inhibition of all three pathways totally eliminated viable blasts. In apoptosis-resistant and apoptosis-sensitive primary AML samples, the three inhibitors all increased apoptosis in vitro after 48 h. Exogenous rhIL-1beta induced the hyperphosphorylation of Bcl-2. It also increased the activation of NF-kappaB in 5/15 blast samples. IL-1beta-mediated survival pathways may be a factor in apoptosis-resistance in primary AML blasts, and may therefore contribute to chemoresistance.
Leukemia 2004 Oct
PMID:Interleukin-1beta maintains an apoptosis-resistant phenotype in the blast cells of acute myeloid leukaemia via multiple pathways. 1530 22

Ceramide is not only structurally but also functionally a key molecule in diverse kinds of sphingolipids. In the past decade, ceramide has been shown to be of crucial significance in several cell functions including apoptosis, cell growth, senescence, and cell cycle control. Among them, the role of ceramide in apoptosis induction has extensively been studied, and ceramide-targeting molecular medicine for apoptosis-based diseases such as malignant tumors, atherosclerosis and neurodegenerative disorders appears to come out to the clinical field. We here describe the recent advances in research of ceramide-mediated apoptosis signaling. We also show the relation of ceramide level through regulation of ceramide-related enzymes (sphingomyelinase, ceramidase, sphingomyelin synthase and glucosylceramide synthase) with diseases such as cancer, leukemia, bacterial infections, AIDS, Alzheimer's disease, atherosclerosis, diabetes mellitus and atopic dermatitis. The strategies to construct the ceramide-targeting medicine for intractable diseases such as cancer and leukemia are discussed.
 ...
PMID:Current status and perspectives in ceramide-targeting molecular medicine. 1602 1