PAK1 is a Therapeutic Target in Acute Myeloid Leukemia and Myelodysplastic Syndrome

ABSTRACT: Poor clinical outcome of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) has been attributed to failure of current chemotherapeutic regimens to target leukemic stem cells. We recently identified p21-activated kinase (PAK1) as a downstream effector molecule of H2.0-like homeobox (HLX), a gene functionally relevant for AML pathogenesis. In this study, we find that inhibition of PAK1 activity by small molecule inhibitors or by RNA interference leads to profound leukemia-inhibitory effects both in vitro and in vivo. Inhibition of PAK1 induces differentiation and apoptosis of AML cells through downregulation of MYC oncogene and a core network of MYC target genes. Moreover, we find that PAK1 up-regulation occurs during disease progression and is relevant for patient survival in M

ORGANISM(S): Homo sapiens

SUBMITTER: Ashley Pandolfi 

PROVIDER: E-GEOD-70791 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress