IDH1, Histone Methylation, and So Forth Virginie Penard-Lacronique, Olivier A. Bernard  Cancer Cell  Volume 30, Issue 2, Pages 192-194 (August 2016) DOI: 10.1016/j.ccell.2016.07.008 Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 Hypothetic Scheme of Development of Acute Myeloblastic Leukemia in Idh1 Knockin Mice IDH1 mutations are present in long-term hematopoietic stem cells (or occur in these cells in humans) and synthetize 2HG. Excess 2HG dysregulates many cellular processes by its mere accumulation and by inhibition of dioxygenases. As far as epigenetics is concerned, it alters the control of methylation (loss of hydroxmethylcytosine; accumulation of cytosine and histone methylation), eventually affecting chromatin structure and gene expression. Note that links have been shown in different models and tissues. Methylated H3K9 on the Atm promoter is associated with closed chromatin structure, decreased expression of the gene, and abnormal DNA repair in LT-HSCs. Dysregulating all these processes facilitates selection of the best-fitted clones and triggers cellular transformation. Cancer Cell 2016 30, 192-194DOI: (10.1016/j.ccell.2016.07.008) Copyright © 2016 Elsevier Inc. Terms and Conditions