Figure 1.

Transcriptional identities correlate with key oncogenic driver events and are agnostic of immunophenotype. A, Study design. 122 normal, noncomplex, and complex karyotype pediatric specimens were selected. Exclusion criteria for sequencing include FAB M3 (acute promyelocytic leukemia, APML), FAB M7 (AMKL), core binding factor (CBF) leukemia (RUNX1–RUNX1T1, CBFB–MYH11), and KMT2Ar cases. Cases underwent WGS, WES, and RNA-seq. Data were combined with four other pediatric data sets, including FAB M7, early T-cell precursor acute lymphoblastic leukemia, the TARGET AML data set, and pediatric mixed phenotype acute leukemia for a total of 435 cases (4,5,7,8,9). Ten additional KMT2Ar AML cases were sequenced to increase the cohort size. Transcriptional clusters as identified by t-SNE, somatic calls, and outcome correlates were utilized to identify biological subtypes as previously described (4). NGS, next-generation sequencing. B, RNA-seq of 435 cases of pediatric AML, AMKL, MPAL, and ETP were combined and batch corrected. t-SNE visualization utilizing the top 100 differentially expressed genes within each data set. Immunophenotype of cases as determined by flow cytometry at diagnosis is shown. AMTL, acute myeloid/T-lymphoblastic leukemia; AUL, acute undifferentiated leukemia; B/M, B-lymphoid and myeloid coexpression; MK, mixed karyotype; T/B, T-lymphoid and B-lymphoid coexpression; T/B/M, T-lymphoid, B-lymphoid, and myeloid coexpression; T/M, T-lymphoid and myeloid coexpression. C, Key oncogenic driver mutations as determined by next-generation sequencing. Ph-like, Philadelphia chromosome–like acute lymphoblastic leukemia; PTD, partial tandem duplication; Txn, transcription.