RNA sequencing of drug-treated cells

MUTZ5, MHH-cALL-4, and TVA-1 cells were cultured in medium containing vehicle, TKI alone, venetoclax alone, or in combination at indicated concentrations for 72 hours. Total RNA was extracted using RNeasy Micro kit (Qiagen) and treated with DNAse, and SMART-seq v4 Ultra Low input RNA kit (Takara) and Nextera XT DNA library prep kit (Illumina) were used for library preparation using 10 ng of total RNA as input. Paired-end sequencing was performed using the Illumina NovaSeq 6000 platform with a 150-bp read length at the Children’s Hospital of Philadelphia. Sequencing reads were aligned to the human genome hg38 reference sequence using STAR v3.5.3a. Samples all had >70% reads mapped to exonic regions and no 3’-bias. Gene-based FPKM and read count matrices were performed with Cufflinks v2.2.1 and featureCounts v1.3.6.