In an ongoing effort to identify roles for chromatin regulators as cancer dependencies, we carried out a negative selection RNAi screen in a cell line derived from a mouse model of high risk B cell acute lymphoblastic leukemia (B-ALL), initiated by introducing the BCR-ABL oncogene into Arf-null bone marrow cells (Williams et al., 2006). The gene discussed is ABL1; the disease is acute lymphoblastic leukemia.