Faculty Opinions recommendation of IDH mutation impairs histone demethylation and results in a block to cell differentiation.

Author(s):  
Michael B Yaffe
2016 ◽  
Author(s):  
Adam D Richarson ◽  
David A Scott ◽  
Olga Zagnitko ◽  
Pedro Aza-Blanc ◽  
Chih-Cheng Chang ◽  
...  

Nature ◽  
2012 ◽  
Vol 483 (7390) ◽  
pp. 474-478 ◽  
Author(s):  
Chao Lu ◽  
Patrick S. Ward ◽  
Gurpreet S. Kapoor ◽  
Dan Rohle ◽  
Sevin Turcan ◽  
...  

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Adam D Richarson ◽  
David A Scott ◽  
Olga Zagnitko ◽  
Pedro Aza-Blanc ◽  
Chih-Cheng Chang ◽  
...  

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from “IDH mutation impairs histone demethylation and results in a block to cell differentiation” by Lu and colleagues, published in Nature in 2012 (Lu et al., 2012). The experiments that will be replicated are those reported in Figures 1B, 2A, 2B, 2D and 4D. Lu and colleagues demonstrated that expression of mutant forms of IDH1 or IDH2 caused global increases in histone methylation and increased levels of 2 hydroxyglutarate (Figure 1B). This was correlated with a block in differentiation (Figures 2A, B and D). This effect appeared to be mediated by the histone demethylase KDM4C (Figure 4D). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Scienceand Science Exchange, and the results of the replications will be published by eLife.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jinxiu Guo ◽  
Ruyue Zhang ◽  
Zhe Yang ◽  
Zhenfeng Duan ◽  
Detao Yin ◽  
...  

Isocitrate dehydrogenase (IDH) is a key metabolic enzyme catalyzing the interconversion of isocitrate to α-ketoglutarate (α-KG). Mutations in IDH lead to loss of normal enzymatic activity and gain of neomorphic activity that irreversibly converts α-KG to 2-hydroxyglutarate (2-HG), which can competitively inhibit a-KG-dependent enzymes, subsequently induces cell metabolic reprograming, inhibits cell differentiation, and initiates cell tumorigenesis. Encouragingly, this phenomenon can be reversed by specific small molecule inhibitors of IDH mutation. At present, small molecular inhibitors of IDH1 and IDH2 mutant have been developed, and promising progress has been made in preclinical and clinical development, showing encouraging results in patients with IDH2 mutant cancers. This review will focus on the biological roles of IDH2 mutation in tumorigenesis, and provide a proof-of-principle for the development and application of IDH2 mutant inhibitors for human cancer treatment.


Author(s):  
H. Alasam

The possibility that intrathymic T-cell differentiation involves stem cell-lymphoid interactions in embryos led us to study the ultrastructure of epithelial cell in normal embryonic thymus. Studies in adult thymus showed that it produces several peptides that induce T-cell differentiation. Several of them have been chemically characterized, such as thymosin α 1, thymopoietin, thymic humoral factor or the serum thymic factor. It was suggested that most of these factors are secreted by populations of A and B-epithelial cells.Embryonic materials were obtained from inbred matings of Swiss Albino mice. Thymuses were disected from embryos 17 days old and prepared for transmission electron microscopy. Our studies showed that embryonic thymus at this stage contains undifferentiated and differentiated epithelial cells, large lymphoblasts, medium and few small lymphocytes (Fig. 5). No differences were found between cortical and medullary epithelial cells, in contrast to the findings of Van Vliet et al,. Epithelial cells were mostly of the A-type with low electron density in both cytoplasm and nucleus. However few B-type with high electron density were also found (Fig. 7).


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