Blood: The IDH1 mutation causes myelin dysplate by interfering with hemolybin synthesis and red blood cell production

Isocric acid dehydrogenase (IDH) mutations are common genetic variants in myelin diseases, including acute myeloid leukemia (AML) and myeloid growth abnormal syndrome (MDS).
genetic variations, including histogeneous and DNA methylation abnormalities, are associated with the pathological aggregation of hematogenic ancestral cells, but it remains unclear whether and how the IDH mutation itself affects hematosis.
the study, researchers found that mice with mutations in the IDH1 gene developed myelin dysploma, which was manifested in anemia, ineffective red blood cell production, childish ancestral cells, and increased red blood cells.
In the red-line cells of these mice, the abnormal metabolite D-2-hydroxypropyt acid (D-2HG) produced by the mutant IDH1 enzyme inhibited the activity of the oxygendic acid dehydrogenase (OGDH), thereby reducing the production of amberyl coenzyme A.
This lack of amberyl coenzyme A inhibits the biosynthesis of hemolybin in hemolytic cells with IDH1 mutations, thereby blocking red line differentiation and red line stereotypes of hematopoietic stem cells (HSCs) at the end of erythra cells, while exogenetic amber coenzyme A or 5-ALA can save red blood cell production in IDH1 mutant red line cells.
deficiency also affects the expression of hemolyxin oxygenase-1 (HO-1), thereby reducing levels of important hemolyte breakdown metabolites such as bilirubin and bilirubin.
these defects can also cause excessive accumulation of reactive oxygen (ROS), leading to the death of IDH1 mutant red line cells.
, the results clearly demonstrate the important role of IDH1 in normal red blood cell production and illustrate how mutations cause myelin disease.
is important for the development of new treatments for IDH mutant tumors.
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