Fig. 1: FG spectrum in pediatric AML.

a A sunburst plot showing all the FGs found in 138 of the 147 pediatric AML patients with suitable materials for FG studies. FGs were detected in 108 of the 138 evaluable cases (78%). FGs in red are novel. One of the NUP98::KDM5A-positive patients had a concurrent PHACTR4::COX10 fusion. R::R, RUNX1::RUNX1T1; P::R, PML::RARA; C::M, CBFB::MYH11; K::M3, KMT2A::MLLT3; N::N, NUP98::NSD1; K::M10, KMT2A::MLLT10; S::M, STIM1::MXD3; S::F, STIM1::F12; NK normal karyotype, CK complex karyotype, C-bZIP CEBPA-basic leucine zipper. b A circos plot showing the novel FGs identified in this study. c Genomic localization of NUP98, STIM1, NSD1, MXD3, and F12 on chromosome 11p15 and 5q35. Red arrows indicate the direction of gene transcription. Cen, centromere. d Schematic diagrams showing STIM1, MXD3, F12, and STIM1 fusion proteins generated by ProteinPaint⁷⁷. Two STIM1::F12 fusions involving the same STIM1 exon (exon 1) but different F12 exons (exons 3 and 5) were identified. e Sanger sequencing confirmed the fusion junctions between STIM1 and the partner genes. f RT-PCR analysis of NUP98::NSD1 and STIM1::MXD3 expression during the disease course of the patient. GAPDH served as the internal control. M size marker, AD at diagnosis, CR first complete remission, PT post-stem cell transplantation, RE AML relapse. g Concurrent STIM1 fusions were associated with impaired immune responses in NUP98::NSD1-positive patients. A bubble plot of GSEA comparing NUP98::NSD1-positive patients with (n = 3) or without (n = 2) concomitant STIM1 fusions. The Gene Ontology biological process and Reactome gene sets were analysed. Remarkably, all the significant gene sets (FDR <0.05 and FWER-adjusted P value <0.05) negatively associated with concurrent STIM1 fusions were related to immune responses. The color of the bubbles indicates the −log10 (FWER-adjusted P value). NES normalized enrichment score.