Compensatory mechanism by TET3 expression and correlation with clinical phenotypes. (A) Bar graphs representing TET2 and TET3 expression (log2_CPM) in TET2 WT (n = 577) MDS patients vs healthy controls (HC, n = 64), ***P < .0001. (B) Schematic representation of the role of L-2-hydroxyglutarate (L2HG) and L2HG dehydrogenase (L2HGDH) in cellular TETs function and global methylation status. (C) L2HGDH mRNA expression levels (log2_CPM) in HC (n = 64), TET2 MT (n = 203), IDH MT (n = 35), and TET2 (n = 577). (D-E) TET2 and TET3 vs L2HGDH mRNA expression (log2_CPM) in TET2 WT patients (n = 577). Kaplan-Meier curves estimate the probability of survival of patients stratified according to uncompensated and compensated TET3 (cutoff, median of expression in the entire cohort) in (F) TET2 MTs (right panel) and all cohort (left panel) and (G) WT cases with low TET2 expression (left panel) and all WT cases (right panel). P values and hazard ratios are depicted in the corresponding panels.