SIRT1 and chronic myelogenous leukemia, BCR-ABL1 positive: Inhibition of SIRT-1 by HDIs causes proliferation reduction of malignant progenitors in CML and decreased drug-resistance to Imatinib (Figure 2.C).44,49,50 Phosphorylation of SIRT-1 during the cell cycle regulates its deacetylase activity.