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

Present day paediatric co-operative group acute lymphoblastic leukaemia (ALL) protocols cure approximately 80% of patients, a result achieved largely through the use of risk-stratified therapies that employ multiple chemotherapy agents. These risk-based therapies utilize host and leukaemia traits to select the most appropriate therapy. However, these risk-stratified approaches predict therapy response imperfectly and an important fraction of patients experience relapse or therapy-related toxicity. Pharmacogenetics, the study of genetic variations in drug-processing genes and individual responses to drugs, may enable the improved identification of patients at higher risk for either disease relapse or chemotherapy-associated side effects. While the impact of genetic variation in the thiopurine-S-methyltransferase gene on ALL treatment outcome and toxicity has been extensively studied, the role of other polymorphisms remains less well known. This review summarizes current research on the impact of genetic variation in drug-processing genes in paediatric ALL and reviews important methodological and statistical issues presently challenging the field of pharmacogenetics.
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PMID:Pharmacogenetic determinants of outcome in acute lymphoblastic leukaemia. 1514 13

Peniciketal A (Pe-A), a spiroketal compound, is isolated from the saline soil-derived fungus Penicillium raistrickii. However, the underlying molecular mechanistic basis for the effects of Pe-A on leukemia is poorly understood. Here, we investigated that Pe-A reduced cell proliferation in three leukemia cell lines (THP-1, K562 and HL60). Importantly, Pe-A showed little cytotoxicity in primary mouse embryonic fibroblast (MEF) cells in a long-duration treatment. For the mechanistic research, we identified 3449 differentially expressed Pe-A-induced proteins through liquid chromatography-tandem mass spectrometry (LC-MS/MS) with TMT label in THP-1 cells. Results showed that many identified proteins were involved in apoptosis and/or autophagy. Then, we confirmed that Pe-A induced not only apoptosis via the mitochondrial pathway but also cytoprotective autophagy by activating the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway indeed. In addition, Pe-A also arrested the cell cycle at the G0-G1 phase by regulating the expressions of checkpoint protein. Collectively, these results provide new insights into the mechanisms that Pe-A may target autophagy-related or apoptosis-related pathways to suppress the development of human leukemia.
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PMID:Effects of a spiroketal compound Peniciketal A and its molecular mechanisms on growth inhibition in human leukemia. 3066 Apr 75