2025
Mis-splicing-derived neoantigens and cognate TCRs in splicing factor mutant leukemias
Kim W, Crosse E, De Neef E, Etxeberria I, Sabio E, Wang E, Bewersdorf J, Lin K, Lu S, Belleville A, Fox N, Castro C, Zhang P, Fujino T, Lewis J, Rahman J, Zhang B, Winick J, Lewis A, Stanley R, DeWolf S, Urben B, Takizawa M, Krause T, Molina H, Chaligne R, Koppikar P, Molldrem J, Gigoux M, Merghoub T, Daniyan A, Chandran S, Greenbaum B, Klebanoff C, Bradley R, Abdel-Wahab O. Mis-splicing-derived neoantigens and cognate TCRs in splicing factor mutant leukemias. Cell 2025, 188: 3422-3440.e24. PMID: 40273911, PMCID: PMC12204805, DOI: 10.1016/j.cell.2025.03.047.Peer-Reviewed Original ResearchConceptsT cell receptorT cellsCurative allogeneic stem cell transplantationVirus-reactive T cellsAllogeneic stem cell transplantationCD8<sup>+</sup> T cellsCognate T cell receptorsStem cell transplantationBlood of patientsImpaired cytotoxic functionPeptide-major histocompatibility complexMyeloid malignanciesCell transplantationActive cancerCytotoxic functionMyeloid leukemiaHealthy donorsPublic neoantigensNeoantigensHistocompatibility complexSplicing alterationsLeukemiaMis-splicing eventsRNA splicing factorsPatients
2023
Transcription Defects in SF3B1K700E Induce Targetable Alterations in the Chromatin Landscape
Boddu P, Gupta A, Roy R, Herrero A, Verma A, Neugebauer K, Pillai M. Transcription Defects in SF3B1K700E Induce Targetable Alterations in the Chromatin Landscape. Blood 2023, 142: 709. DOI: 10.1182/blood-2023-188083.Peer-Reviewed Original ResearchChromatin organizationSuch epigenetic changesGenome editing approachesRNA splicing factorsChromatin landscapeSingle mutant alleleEpigenetic landscapeGenomic integrityTranscription defectTranscription kineticsSplicing factorsChIP-seqEpigenetic regulatorsEpigenetic changesEpigenetic therapyMutant allelesEditing approachesFactor mutationsK562 cell lineDownstream effectsCell linesMyeloid disordersClonal myeloid disordersHDAC pathwayMutations
2022
Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells
North K, Benbarche S, Liu B, Pangallo J, Chen S, Stahl M, Bewersdorf J, Stanley R, Erickson C, Cho H, Pineda J, Thomas J, Polaski J, Belleville A, Gabel A, Udy D, Humbert O, Kiem H, Abdel-Wahab O, Bradley R. Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells. Nature Biotechnology 2022, 40: 1103-1113. PMID: 35241838, PMCID: PMC9288984, DOI: 10.1038/s41587-022-01224-2.Peer-Reviewed Original ResearchConceptsBreast cancerExpression of herpes simplex virus thymidine kinaseHerpes simplex virus thymidine kinaseCancer cellsPancreatic cancer cells in vitroWild-type cellsCancer cells in vitroCancer gene therapyTargeting of cancer cellsTumor-specific changesUveal melanoma cellsTreatment in vivoSynthetic intronChange-of-function mutationsCells in vitroUveal melanomaSF3B1 mutationsHSV-TKGene therapyTumor cellsIsogenic wild-type cellsMelanoma cellsRNA splicing factorsCancerHost survival
2021
Modulation of RNA Splicing Enhances Response to BCL2 Inhibition in Acute Myeloid Leukemia
Wang E, Pineda J, Bourcier J, Stahl M, Penson A, Wakiro I, Singer M, Cui D, Erickson C, Knorr K, Stanley R, Chen X, McMillan E, Bossard C, Aifantis I, Bradley R, Abdel-Wahab O. Modulation of RNA Splicing Enhances Response to BCL2 Inhibition in Acute Myeloid Leukemia. Blood 2021, 138: 507. DOI: 10.1182/blood-2021-146373.Peer-Reviewed Original ResearchCdc2-like kinasePre-mRNA splicingRNA splicing factorsSplicing factorsRNA processingAcute myeloid leukemiaRNA splicingBCL2 inhibitionGenetic screeningPhosphorylation of splicing factorsRegulate pre-mRNA splicingModulates RNA splicingSR protein functionResistance to therapyAntiapoptotic protein Bcl-2Overcome venetoclax resistanceRNA processing factorsDrug responseAML drugsGenome-wide CRISPR/Cas9 screenEntity's Board of DirectorsDrug-gene interactionsProtein Bcl-2Treated AML cellsAnti-apoptotic factors
2017
Abstract 5020: A genome-scale ORF screen reveals an alternative splicing program that regulates mesenchymal and stem-like cell states in breast cancer
Li J, Choi P, Chaffer C, Labella K, Kim J, Doench J, Dai C, Giacomelli A, Ly S, Hwang J, Hong A, Ilic N, Gjoerup O, Meyerson M, Brooks A, Weinberg R, Hahn W. Abstract 5020: A genome-scale ORF screen reveals an alternative splicing program that regulates mesenchymal and stem-like cell states in breast cancer. Cancer Research 2017, 77: 5020-5020. DOI: 10.1158/1538-7445.am2017-5020.Peer-Reviewed Original ResearchAlternative splicing programFilamin BSplicing factorsGene Set Enrichment AnalysisAlternative splicingCell statesSplicing programCD44 cell surface markersRegulation of EMTShort isoformStem-like stateDownstream targetsStem cell fate determinationCell fate determinationRNA splicing factorsHuman mammary epithelial cellsBreast cancer patient samplesMammary epithelial cellsBreast cancer cell linesRNA sequencing analysisTumor formation in vivoAssociated with stem cell propertiesBasal-like breast cancerCancer patient samplesStem-like traits
2014
Bone Marrow Microenvironment Regulates Alternative Splicing Events in Myeloma Cells through Downregulation of RNA Binding Protein Fox2
Song W, Zhang C, Hu Y, Gkotzamanidou M, Shah P, Shan W, Yang G, Li Y, Sperling A, Rashid N, Samur M, Amin S, Tai Y, Hideshima T, Parmigiani G, Magrangeas F, Minvielle S, Avet-Loiseau H, Anderson K, Li C, Munshi N. Bone Marrow Microenvironment Regulates Alternative Splicing Events in Myeloma Cells through Downregulation of RNA Binding Protein Fox2. Blood 2014, 124: 4714. DOI: 10.1182/blood.v124.21.4714.4714.Peer-Reviewed Original ResearchRNA binding proteinRNA-seq dataAlternative splicingSplicing factorsActin polymerizationCell linesNon-protein coding RNAsIsoform switchBinding proteinDiversity of transcriptomesMM cell linesRNA alternative splicingAlternative splicing eventsImportant RNA binding proteinRNA splicing factorsRNA-seq analysisPredominant nuclear localizationGene enrichment analysisCytoskeleton regulationGene regulationStromal cell interactionsSplicing eventsCoding RNAsQ-PCR analysisImportant genes
2013
Expression Of Mutant Spliceosomal Protein SF3B1 Results In Dysregulated Hematopoietic Maturation
Minella A, Ramirez O, Xu Y, Murthy T, Yang X, Pillai M. Expression Of Mutant Spliceosomal Protein SF3B1 Results In Dysregulated Hematopoietic Maturation. Blood 2013, 122: 2773. DOI: 10.1182/blood.v122.21.2773.2773.Peer-Reviewed Original ResearchSplicing of RNAErythroid maturationErythroid differentiationRNA splicing factorsMurine progenitor cellsMyelodysplastic syndromeWhole-genome sequencingSpliceosomal proteinsSplicing factorsColony forming assaysMutant SF3B1SF3B1 mutationsHematopoietic maturationCDNA constructsHuman cord bloodComplementary experimental approachesAddition of erythropoietinHematopoietic precursor cellsGenome sequencingMDS patientsMolecular mechanismsPosition 700Accessory receptorsHematopoietic progenitorsNormal hematopoiesis
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