Glutathione S-transferases (GSTs) are phase II detoxification enzymes involved in the metabolism of carcinogens and anticancer drugs, known also to interact with kinase complexes during oxidative or chemical stress-induced apoptosis. We were interested whether their polymorphic variants may account for differences in outcome of patients with acute myeloid leukemia (AML) following chemotherapy. We studied the prognostic role of polymorphisms in three GST genes (GSTP1/M1/T1) in a large patient cohort of the German Austrian Acute Myeloid Leukemia Study Group, treated according to prospective multicenter clinical trials (AML HD98A: 254 patients; AML HD98-B: 100 patients), with a median follow-up of 46 months. Looking at short-term adverse drug reactions, homozygous carriers of the GSTP1*105 Val allele had a faster neutrophil and platelet recovery (P=0.002 and 0.02, respectively) and a reduced need of red cell and platelet transfusions (P=0.01 and 0.03, respectively). Response to induction chemotherapy did not vary according to GST polymorphisms. Multivariable Cox regression models revealed a significant better relapse-free (RFS) and overall survival for the GSTP1(*)105 Val (P=0.003 and 0.03, respectively), whereas GSTT1 and GSTM1 genotypes had no significant impact. The favorable impact of GSTP1(*)105 Val on RFS seems to be restricted to the subgroup of patients exhibiting a normal karyotype.
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http://dx.doi.org/10.1038/leu.2008.169 | DOI Listing |
Anticancer Res
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Department of Hematology/Oncology, Luminis Health Anne Arundel Medical Center, Annapolis, MD, U.S.A.
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Poult Sci
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Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand, 10330; Center of Excellence for Emerging and Re-emerging Infectious Diseases in Animals (CUEIDAs), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand, 10330; Center of Excellence in Animal Vector-Borne Diseases, Veterinary Parasitology Unit, Department of Veterinary Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand, 10330; Center of Excellence of Systems Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 10330. Electronic address:
Duck Tembusu virus (DTMUV), an emerging avian pathogenic flavivirus, is notably associated with neurological disorders and acute egg drop syndrome in ducks. We previously demonstrated that the susceptibility of ducks to DTMUV infection varies significantly with age, with younger ducks (4-week-old) exhibiting more severe disease than older ducks (27-week-old). However, the immunological mechanisms underlying these age-related differences in disease severity remain unclear.
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Department of Hematology, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel.
Molecular assessment of measurable residual disease (MRD) in NPM1-mutated AML patients is a powerful prognostic tool to identify the risk of relapse. There is limited data regarding MRD-guided decisions against alloSCT in elderly patients and FLT3-ITD co-mutation. We describe the outcome of NPM1-mutated AML patients in whom alloSCT was deferred based on ELN 2017 risk and MRD response.
View Article and Find Full Text PDFPLoS One
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Department of Clinical Laboratory, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan.
Differentiation therapy with all-trans retinoic acid (ATRA) is well established for acute promyelocytic leukemia (APL). However, the narrow application and tolerance development of ATRA remain to be improved. A number of kinase inhibitors have been reported to induce cell differentiation.
View Article and Find Full Text PDFCancer Med
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Gynaecological Cancer Research Group, Lowy Cancer Research Centre, School of Clinical Medicine, Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales, Australia.
Objective: Endometrial cancer is one of the few cancers for which mortality is still increasing. A lack of treatment options remains a major challenge, particularly for some subtypes of the disease. GZD824, also known as olverembatinib, is a multi-kinase inhibitor previously investigated in clinical trials for chronic myeloid leukaemia and Ph+ acute lymphoblastic leukaemia as a BCR-ABL inhibitor.
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