CDK4 and acute myeloid leukemia: For the mechanisms of synergistic effect, we found that HHT combined with ibrutinib induced simultaneous up-regulation of PARP, Caspases, γH2AX, P53, P21 WAF1/CIP1 and down-regulation of CCND2, CCND3, CDK4, 6, 2, P-AKT, P-STAT5/Pim-2/C-Myc and Bcl-2 family at the protein level in FLT3-ITD mutant AML cells.