A novel covalent inhibitor of CDK7 synergizes with Venetoclax in acute myeloid leukemia

To assess the synergistic effects of CDK7 inhibitor with Venetoclax, we performed RNA sequencing and gene set enrichment analysis using Venetoclax sensitive and resistant model systems. RNA-sequencing from paired Venetoclax-sensitive and Venetoclax-resistant cells treated with CDK7 inhibitor showed downregulation of genes involved in proliferation and apoptosis. CDK7 inhibitor induces apoptosis in AML cells and combined treatment with Venetoclax led to synergistic effects in overcoming resistance. We have labeled parental Venetoclax-sensitive MOLM13 cells with CDK7 inhibitor treatment PT while untreated cells were marked as PU. Similarly, Venetoclax-resistant MOLM13 cells with and without CDK7 inhibitor treatment were labeled as RT and RU respectively. cDNA libraries in duplicates from PT, PU RT and RU were pooled and diluted to final optimal loading concentration before cluster amplification on the Illumina flow cell. Once the cluster generation is completed, the clustered flow cell is loaded on Illumina HiSeq X instrument to generate 167 million, 150bp paired end reads per sample. Image analysis, base calling, and quality check was performed with Illumina data analysis pipeline RTA v1.18.64. RNAseq reads were provided in compressed Sanger FASTQ format.