AML samples exhibited deregulated TOE1 expression versus normal hematopoietic stem/progenitor cells (HSPCs), and TOE1 depletion suppressed the proliferation of myeloid leukemia cell lines, and primary human HSPCs, partly through a p21-activated-kinase 2 (PAK2) mediated mechanism. Here, PAK2 is linked to myeloid leukemia.