Figure 1.

Cartoon depicts the cross talk between various components of the core clock mechanism and the stabilizing loops (Rev-erbs and RORs) that drive daily system-wide rhythms in gene expression and metabolites. Also shown are the three core-metabolic sensing pathways—AMP-activated kinase (AMPK), Myc, and SIRTs. NAD⁺ feedsback to control the clock by regulating the function of class III histone deacetylases—the Sirtuins. The SIRTs and core clock components regulate Myc expression that competes with BMAL1:CLOCK on transcription targets sites and also drives Rev-erb expression. Colored components within the cartoon highlight the factors linked to hematological malignancies such as acute myeloid leukemia, chronic myeloid leukemia, and diffuse large B-cell lymphoma.