Review Article

Myeloid Neoplasias: What Molecular Analyses Are Telling Us

Figure 2

Molecular-metabolic pathways involved in myeloid neoplasias. (a) MPL and JAK2 cytoplasmic levels are controlled by ubiquitin (ub) CBL activity inducing protein degradation via proteasome. (b) IDH1/2 wild-type enzymes convert isocitrate to α-ketoglutarate (α-KG), a TET2 cofactor. IDH1/2 mutations catalyze α-KG conversion to 2-hydroxyglutarate (2-HG) oncometabolite. (c) Alterations in TET2 and DNMT enzymes lead to methylation deregulation leading to hypomethylation. ASXL1 and EZH2 loss-of-function affect chromatin structure favoring a relaxed state. These modifications increase gene transcription.
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