Cancer

Cell culture and mouse studies suggest inhibiting the mRNA-decapping enzyme DCPS could help treat AML. Screening of a CRISPR single-guide RNA (sgRNA) library targeting protein-coding genes and miRNAs in two mouse AML cell lines expressing CRISPR-associated protein 9 (Cas9) identified DCPS as a gene whose knockout decreased cell viability compared with non-targeting sgRNA. In four human AML cell lines, shRNA targeting DCPS or the DCPS inhibitor PF-06687859 decreased proliferation compared with scrambled shRNA or vehicle, respectively. In one of the AML cell lines, the shRNA targeting DCPS or PF-06687859 increased cell cycle arrest and apoptosis. In three patient-derived xenograft (PDX) mouse models of AML, PF-06687859 decreased leukemia burden in the peripheral blood and bone marrow and increased survival compared with vehicle. Next steps could include testing inhibitors of DCPS in additional models of AML...