Oncogene withdrawal results in loss of leukemia self-renewal gene-expression signatures. (A-D) GSEA analysis reveals loss of previously published gene-expression signatures. (A) The Krivtsov et al leukemia self-renewal gene-expression signature which was derived by identifying a set of genes common to self-renewing hematopoietic subsets (L-GMPs and HSCs).¹⁴  (B) The NRAS^G12D-directed nonleukemic HSC self-renewal signature.⁹  (C) The MLL-AF9–directed leukemia self-renewal gene-expression program.¹⁶  (D) The MLL fusion protein signature of primary human leukemias.²³  (E) NRAS^G12V-On and -off gene-expression data from our study and self-renewing (HSC and L-GMP) and non–self-renewing (GMP) expression data from the Krivtsov et al¹⁴  study were compared. Each individual data set was independently transformed relative to the average value for the data set and both data sets were then merged. The probe sets of the self-renewing gene-expression signature defined by Krivtsov et al¹⁴  were used for unsupervised, 2-dimensional, hierarchical clustering of these merged data sets. (F) NRAS^G12V-On and -Off samples from our study and MLL-AF9-On and -Off samples from Zuber et al¹⁶  were independently transformed relative to the oncogene-on state in each data set and both data sets were then merged. The gene list from the MLL-AF9–directed leukemia self-renewal signature was used for unsupervised, 2-dimensional, hierarchical clustering of these merged data sets.