Kaplan-Meier estimates of RFS using the combined gene expression classifier for RFS and flow cytometric measures of MRD in the presence of kinase signatures, JAK mutations, and IKAROS/IKZF1 deletions. (A-B) Application of the original 42-probe-set (38-gene; supplemental Table 4) gene expression classifier for RFS combined with end-induction flow cytometric measures of MRD distinguishes 2 distinct risk groups in COG 9906 ALL patients with kinase signatures (A) and 3 risk groups in those patients lacking kinase signatures (B). (C-D) Application of the combined classifier also resolves 2 distinct and statistically significant risk groups in ALL patients with JAK mutations (C) and in 3 risk groups in those patients lacking JAK mutations (D). (E-F) Application of the combined classifier distinguishes 3 risk groups with statistically significant RFS and patients with (E) and without IKAROS/IKZF1 deletions. The P value reported in the lower left corner corresponds to the log rank test for differences among all groups.