BCL2/BCL-XL gene expression analysis identifies diverse subtypes across ALLs linked to specific genetic aberrations. (A) Gene expression profile’s landscape of the BCL2/BCL-XL in the ALL subtypes illustrated in a 2-dimensional t-distributed stochastic neighbor embedding (tSNE) map. Gene expression profiles of BCL2 and BCL-XL genes in B- and T-ALL were analyzed using a bioinformatical approach and RNA-seq data from leukemic cells of 1976 (1418 B-ALL and 558 T-ALL) and 916 (780 B-ALL and 136 T-ALL) patients diagnosed with ALL. Gene expression profiles were evaluated and analyzed using hierarchical clustering, tSNE analysis, and predictive modeling using cases of known subtypes, as previously described.³³ Gene expression signal is displayed in log₂. (B) Association of clusters based on the t-SNE map with subtypes shown for comparison with the hierarchical clustering approach. Cohort metrics defining BCL2 activity profiles to genetic abnormalities consists of 23 different B-ALL subtypes clustered based on known chromosomal abnormalities and genetic mutations as follows: BCL2/Myc, Mef2D, Tcf3-Px1, Hlf, Pax5alt, other, Dux4, Kmt2a-like, Nutm1, Ikzf1 N159Y, Ph-like, Ph, ETV6-Tunx1–like, low hypodiploid, Pax5 P80R, ETC6Runx1, Clrf2 (non–Ph-like), near haploid, iAMP21, low hyperdiploidy, Znf384, Kmt2a, Znf384-like, and high hyperdiploidy. (C) Association of the clusters based on the t-SNE map with the subtypes shown for comparison with the hierarchical clustering approach. Cohort metrics defining BCL2 activity profiles to genetic abnormalities consists of 14 different T-ALL subtypes clustered based on known chromosomal abnormalities and genetic mutations, as follows: LMO1/2, TAL1, TAL2, TLX1, TLX3, HOXA, NKX2-1, DDX3-MLLT10, PICALM-MLLT10, KMT2A, and Spi1. (D) BCL-XL activity across different B-ALL subtypes. (E) BCL-XL activity across different T-ALL subtypes.