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Palamarchuk A Yan PS Zanesi N Wang L Rodrigues B Murphy M Balatti V Bottoni A Nazaryan N Alder H Rassenti L Kipps TJ Freitas M Croce CM Pekarsky Y 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(7):2555-2560
B-cell chronic lymphocytic leukemia (CLL) is the most common human leukemia. Deregulation of the T-cell leukemia/lymphoma 1 oncogene (TCL1) in mouse B cells causes a CD5(+) leukemia similar to aggressive human CLL. To examine the mechanisms by which Tcl1 protein exerts its oncogenic activity in B cells, we performed proteomics experiments to identify its interacting partners. We found that Tcl1 physically interacts with de novo DNA methylthansferases Dnmt3A and Dnmt3B. We further investigated the effects of Tcl1 up-regulation on the enzymatic activity of Dnmt3A and found that Tcl1 overexpression drastically inhibits Dnmt3A function. In addition, B cells from TCL1 transgenic mice showed a significant decrease in DNA methylation compared with WT controls. Similarly, CLL samples with high Tcl1 expression showed a decrease in DNA methylation compared with CLL samples with low Tcl1 expression. Given the previous reports of inactivating mutations of DNMT3A in acute myelogenous leukemia and myelodysplastic syndrome, our results suggest that inhibition of de novo DNA methylation may be a common oncogenic mechanism in leukemogenesis. 相似文献
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Yuri A. Saito Joseph J. Larson Elizabeth J. Atkinson Euijung Ryu Ann E. Almazar Gloria M. Petersen Nicholas J. Talley 《Digestive diseases and sciences》2012,57(10):2650-2657
Background
Smaller studies have evaluated SLC6A4 5-HTTLPR and GNβ3 825C>T polymorphisms in IBS, and interactions between 5-HTT LPR with life events have been reported in the psychiatric literature, but gene–environment studies in IBS are lacking.Aims
The purpose of this study was to assess the association of two polymorphisms with IBS and age of onset, and whether there are gene–environment interactions with IBS.Methods
Outpatients with IBS and controls completed a validated questionnaire and provided blood for DNA. Comparisons of genotype/allele frequencies between cases and controls were performed with logistic regression. Linear regression was used to evaluate the association between the variants and age of onset. Environmental variables tested included abuse, parental alcohol abuse, parental psychiatric disorders, and gastrointestinal infections.Results
Genotyping was performed in 385 cases and 262 controls with median age of 50 years (range, 18.0–70.0) and 498 (77 %) females. The IBS subtype distribution among cases was: 102 (26 %) D-IBS, 40 (10 %) C-IBS, 125 (32 %) M-IBS, 118 (31 %) other. No association was observed between IBS or age of onset and both variants. Significant interactions were observed between GI infection and the GNβ3 825T allele. For those reporting gastrointestinal infection, the OR for IBS was 3.9 (95 % CI 1.2–12.7) whereas the OR was 0.86 (95 % CI 0.65–1.13) for those without prior infection.Conclusions
There was a significant interaction between the GNβ3 polymorphism and infection in the development of IBS, suggesting that its etiology is the result of a combination of specific genetic and environmental risk factors. 相似文献86.
Armen?Yuri?Gasparyan Giuseppe?CoccoEmail author Stefano?Pandolfi 《Rheumatology international》2012,32(2):461-464
Cardiovascular disease is the leading cause of premature mortality in patients with rheumatoid arthritis (RA). Pathophysiology
of rheumatoid cardiovascular phenomenon is not fully understood, but systemic inflammation is thought to play a crucial role
in the endothelial damage and accelerated course of atherosclerotic disease. Rheumatoid inflammation can also cause coronary
pathology and heart failure. We present a case of transient cardiomyopathy in RA in the absence of occlusive coronary pathology,
which mimics acute coronary syndrome. 相似文献
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