biostudies-literatureClosa AEuropean Union: ERDF/ESFMinisterio de Ciencia, Innovación y UniversidadesEllen Weisberg Fund: Advancing Breakthroughs in Pediatric CancerSpanish Ministry of Science and InnovationGETNE2019 ResearchUniversidad de Córdoba-FEDERNCI NIH HHSNational Institutes of HealthJunta de AndalucíaCIBERobn Fisiopatología de la Obesidad y NutriciónEMBL Australiazcac041https://www.ebi.ac.uk/biostudies/studies/S-EPMC9732526biostudies-literatureUnknown4(4)A significant proportion of infant B-cell acute lymphoblastic leukemia (B-ALL) patients remains with a dismal prognosis due to yet undetermined mechanisms. We performed a comprehensive multicohort analysis of gene expression, gene fusions, and RNA splicing alterations to uncover molecular signatures potentially linked to the observed poor outcome. We identified 87 fusions with significant allele frequency across patients and shared functional impacts, suggesting common mechanisms across fusions. We further identified a gene expression signature that predicts high risk independently of the gene fusion background and includes the upregulation of the splicing factor <i>SRRM1</i>. Experiments in B-ALL cell lines provided further evidence for the role of SRRM1 on cell survival, proliferation, aNAR cancerA convergent malignant phenotype in B-cell acute lymphoblastic leukemia involving the splicing factor SRRM1.PMC9732526BIO2017-85364-RBIO-0139PID2019-105201RB-I00UCO-202099901918904U01 CA232563Torres-Diz MHayer KEAdriaanse FRSCastano JPLuque RMEyras EClosa AMelero JLBos RSRoberts KGFuentes-Fayos ACThomas-Tikhonenko AHunger SPReixachs-Sole MMullighan CGStam RWfalseA convergent malignant phenotype in B-cell acute lymphoblastic leukemia involving the splicing factor SRRM1.A significant proportion of infant B-cell acute lymphoblastic leukemia (B-ALL) patients remains with a dismal prognosis due to yet undetermined mechanisms. We performed a comprehensive multicohort analysis of gene expression, gene fusions, and RNA splicing alterations to uncover molecular signatures potentially linked to the observed poor outcome. We identified 87 fusions with significant allele frequency across patients and shared functional impacts, suggesting common mechanisms across fusions. We further identified a gene expression signature that predicts high risk independently of the gene fusion background and includes the upregulation of the splicing factor <i>SRRM1</i>. Experiments in B-ALL cell lines provided further evidence for the role of SRRM1 on cell survival, proliferation, a2022-01-01T00:00:00Z2022 Dec2026-04-08T11:32:08.192Z2024-11-07T00:51:40.98ZS-EPMC97325263651852710.1093/narcan/zcac041