Fig. 3

CDK7 inhibition modulates cell cycle by targeting cell cycle checkpoints. A Dose dependent decrease in expression of c-Myc and increase in p53 and p21 after 6 h of XL102 treatment in leukemic cells. B Decrease in expression of c-Myc in patient derived AML blasts after 24 h of 1 μM XL102 treatment C Cell-cycle analysis was performed analysis using flow cytometry on MOLM13 and OCI AML2 cells treated with XL102 for 24 h. The data showed increase in population of cells in G1 phase and significant decrease in S phase after treatment. The changes in cell-cycle distribution were significant in both cell lines (MOLM13, P = 0.0005; OCI AML2, P = 0.0021) D Decrease in expression p-CDK1 (Thr-161) and p-CDK2 (Thr-160) in OCI AML2 & MOLM13 cells after 6 h and 24 h of XL102 treatment. E Cell-cycle analysis was performed using flow cytometry on MOLM13 after serum starvation for 24 h and mimosine treatment (40 μM) followed by 24 h of XL102 treatment. F Schematic representation of c-Myc/p53 axis. G CRISPR/Cas9 genome editing tool was utilized to performed c-Myc knockout (c-Myc^KO) using sgRNA targeting c-Myc in MOLM13 cells. The downstream targets such as p21,p27, CyclinD were analyzed along with expression of CDK7 H Cell cycle suppression in Myc^KO cells in comparison to control. I Genetic depletion of CDK7 using CRISPR/Cas9 and analysis of downstream targets J Cell cycle suppression in CDK7^KO cells in comparison to control