To probe the dependence of PPM1D activity on p53, we performed a CRISPR/Cas9 resistance screen in a human AML cell line and found that inhibition of PPM1D by GSK2830371 resulted in strong selection of sgRNAs targeting TP53, suggesting that PPM1D inhibition requires p53 for effects on cellular proliferation. Here, PPM1D is linked to acute myeloid leukemia.