Cancers, Vol. 12, Pages 2427: Isocitrate Dehydrogenase Mutations in Myelodysplastic Syndromes and in Acute Myeloid Leukemias

Cancers, Vol. 12, Pages 2427: Isocitrate Dehydrogenase Mutations in Myelodysplastic Syndromes and in Acute Myeloid Leukemias Cancers doi: 10.3390/cancers12092427 Authors: Ugo Testa Germana Castelli Elvira Pelosi Acute myeloid leukemia (AML) is a heterogeneous disease generated by the acquisition of multiple genetic and epigenetic aberrations which impair the proliferation and differentiation of hematopoietic progenitors and precursors. In the last years, there has been a dramatic improvement in the understanding of the molecular alterations driving cellular signaling and biochemical changes determining the survival advantage, stimulation of proliferation, and impairment of cellular differentiation of leukemic cells. These molecular alterations influence clinical outcomes and provide potential targets for drug development. Among these alterations, an important role is played by two mutant enzymes of the citric acid cycle, isocitrate dehydrogenase (IDH), IDH1 and IDH2, occurring in about 20% of AMLs, which leads to the production of an oncogenic metabolite R-2-hydroxy-glutarate (R-2-HG); this causes a DNA hypermethylation and an inhibition of hematopoietic stem cell differentiation. IDH mutations differentially affect prognosis of AML patients following the location of the mutation and other co-occurring genomic abnormalities. Recently, the development of novel therapies based on the specific targeting of mutant IDH may contribute to new effective treatments of thes...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research