On the molecular level, L1CAM, a marker for glioma stem cells, was among the genes that was persistently upregulated despite long-term loss of mtIDH1 expression, and L1CAM is associated with gliomagenesis in xenograft models.44 In clinical studies with mtIDH1/2 inhibitors in IDH1/2mt AML patients, potent suppression of D-2-HG is sometimes observed without epigenetic demethylation. Here, IDH1 is linked to acute myeloid leukemia.