ABSTRACT
Hypomethylating agents may be of interest in the context of carboxypeptidase G island methylator phenotype hypermethylation phenotype induced by Isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations. In vitro and in vivo preclinical studies have demonstrated that inhibition of IDH1/2-mutant enzymes decrease intracellular D-2-hydroxyglutarate levels, reverse epigenetic dysregulation and release the differentiation block. IDH1 and IDH2 mutations are heterozygous, missense mutations leading to the substitution of the amino acids arginine 132 in IDH1 and arginine 172 or 140 in IDH2. Hypermethylation is the dominant feature of IDH1/2-mutant acute myeloid leukemias and these mutants display similar DNA methylation profiles. Dermatan sulfate is a life-threatening complication of uncertain pathogenesis that can occur during the treatment of acute promyelocytic leukemia by ATRA and/or arsenic trioxide. Pathophysiology is still elusive but is related to the process of blasts differentiation induced by ATO and/or ATRA. Discontinuation of ATRA is required and efficient in case of rapidly worsening situation and/or severe presentation.
