Hierarchical clustering and schematic representation of ZNF384 proteins. (A) Hierarchical clustering based on RNA-seq gene-expression data. A total of 117 B-other, 9 ETV6-RUNX1–positive, and 2 BCR-ABL1–positive ALL/MPAL cases were clustered hierarchically (vst normalization, ward.D method, and Euclidean distance linkage for hierarchical clustering) based on the expression of the most variably expressed transcripts (transcripts with standard deviation of expression ≥35% of the maximal standard deviation; n = 391). The resulting dendrogram is shown. ALL was classified as BCR-ABL1-like and ETV6-RUNX1-like based on coclustering with BCR-ABL1–positive and ETV6-RUNX1–positive ALL, respectively, in supervised HCA.⁶  Classification into genetically defined subtypes was based on the identification of defining genetic lesions. The cohort consists of 110 patients as reported previously,⁶  complemented by 7 additional patients with ZNF384 gene aberrations and available RNA-seq data. B-rest, not classified into any established subtype; iamp, intrachromosomal amplification; AMP, amplification. (B) Schematic representation of the wild-type ZNF384 protein with the positions of 3 novel aberrations and chimeric proteins encoded by canonical ZNF384 fusion and the novel ZNF384-TEX41 fusion. LZ, leucine-rich domain; NLS, nuclear localization signal; PR, proline-rich domain; QA, Gln-Ala repeat; SR, serine-rich domain; ZFs, Kruppel-type C2H2 zinc-finger domains. Adapted from Liu et al⁵  with permission.