Model of AML1-ETO leukemogenesis through the p21^WAF1 pathway. Here we propose a model whereby the bypass of the p21^WAF1-regulated pathway(s) cooperates with AML1-ETO in promoting leukemia development. Specifically, in the presence of p21^WAF1 AML1-ETO ability to promote leukemia is limited by p21^WAF1 role in growth regulation, genome stability, regulating transcription networks, and in primary cells' apoptosis evasion. However, both p21^WAF1 and AML1-ETO regulate stem cell maintenance and expansion. The loss of p21^WAF1 role in growth regulation, DNA repair, and regulation of transcription establishes an advantageous situation for leukemia development.