Presence of activating RAS mutations renders cells resistant to JMJD1C loss. Fold change in JMJD1C sgRNA abundance (A)⁵⁶  and ATARIS score (B)⁵⁵  in leukemia cell lines. Cell lines in blue bear RAS mutations according to the Broad Institute Cancer Cell Line Encyclopedia. (C) MOLM13, MOMO-MAC-1, NOMO1, THP1, U937, and OCI-AML3 cells were infected with the indicated sgRNA-Cas9-TdTomato viruses and subjected to flow cytometry analysis over a period of 28 days. Fold changes in TdTomato positivity compared with day 3 are plotted. Data are mean ± standard deviation of independently transduced triplicate samples. (D) Fold depletion of sgRNAs in MOLM13 cells overexpressing NRAS^G12V and in mouse MLL-AF9-Cas9 cells overexpressing NRAS^G12V and KRAS^G12D. Data are mean ± standard deviation of independently transduced triplicate samples. (E) Western blotting of NRAS/KRAS expression in cells in panel D.