PFKM and T-cell acute lymphoblastic leukemia: As noted above, in human T-cell acute lymphoblastic leukemia cells, the closely related cyclin D3 protein (in complex with Cdk6) phosphorylates and inhibits the activity of two key enzymes in the glycolytic pathway, PFK1 and pyruvate kinase M2, thereby inhibiting glycolysis and redirecting glucose metabolites into the PPP; importantly, cyclin D1/Cdk4 did not have this effect (36).