Whole exome sequencing and data analysis

Genomic DNA of ZM-induced primary tumors, derived from bone marrow of leukemic mice and followed by a quick puromycin selection to enrich ZM-expressing leukemic blasts, was extracted using the PureLink Genomic DNA Mini Kit (Invitrogen, cat# K182002). Genomic DNA of the ZM-infected HSPCs, which were used in bone marrow transplantation for inducing AML in mice, was used as control for calling potential spontaneous mutations acquired during the course of AML development in vivo. Library preparation, sequencing, and data analysis were carried out by Novogene. In brief, sequencing libraries were generated using the Agilent SureSelectXT Mouse All Exon kit. After 100X whole exome sequencing, BWA was utilized to map the paired-end clean reads to the mouse reference genome mm10. SNPs and InDels were detected and filtered (total counts ≥ 10) using GATK software. The tool muTect and Strelka were used to call somatic SNPs and InDels in tumor samples, respectively. Variants were annotated with ANNOVAR.