Our system could be used to address whether these findings can be translated to human HSPCs by achieving site specific HR that would simultaneously knock out a tumor suppressor (e.g. TP53) and drive mutant KRAS under endogenous regulatory conditions, instead of using strong constitutive exogenous viral promoters with little control over proviral copy number and heterogeneity of transgene expression. This evidence concerns the gene TP53 and neoplasm.