SF3B1 mutation–mediated sensitization to H3B-8800 splicing inhibitor in chronic lymphocytic leukemia

Understanding the pathogenic mechanisms of SF3B1 mutation can help unravel their contribution in patients’ worse prognosis. The cytotoxic effects and delayed leukemic infiltration induced by H3B-8800 support the potential use of SF3B1 inhibitors as a novel therapy in CLL.

[1]  F. Bosch,et al.  Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY , 2022, Leukemia.

[2]  Andrew J. Dunford,et al.  Molecular map of chronic lymphocytic leukemia and its impact on outcome , 2022, Nature Genetics.

[3]  C. Plass,et al.  Altered DNA Methylation Profiles in SF3B1 Mutated CLL Patients , 2021, International journal of molecular sciences.

[4]  I. Flinn,et al.  Phase I First-in-Human Dose Escalation Study of the oral SF3B1 modulator H3B-8800 in myeloid neoplasms , 2021, Leukemia.

[5]  Y. Wan,et al.  Characterization of the aberrant splicing of MAP3K7 induced by cancer-associated SF3B1 mutation. , 2021, Journal of biochemistry.

[6]  O. Abdel-Wahab,et al.  The Effect of SF3B1 Mutation on the DNA Damage Response and Nonsense-Mediated mRNA Decay in Cancer , 2021, Frontiers in Oncology.

[7]  E. Campo,et al.  IGLV3-21R110 identifies an aggressive biological subtype of chronic lymphocytic leukemia with intermediate epigenetics. , 2020, Blood.

[8]  F. Pozzo,et al.  SF3B1-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation. , 2020, Haematologica.

[9]  S. Chandarlapaty,et al.  Mutant SF3B1 promotes AKT and NF-kB driven mammary tumorigenesis. , 2020, The Journal of clinical investigation.

[10]  O. Abdel-Wahab,et al.  Single-cell genomics reveals the genetic and molecular bases for escape from mutational epistasis in myeloid neoplasms. , 2020, Blood.

[11]  R. Rabadán,et al.  SF3B1 mutant-induced missplicing of MAP3K7 causes anemia in myelodysplastic syndromes , 2020, Proceedings of the National Academy of Sciences.

[12]  T. Aittokallio,et al.  SynergyFinder 2.0: visual analytics of multi-drug combination synergies , 2020, Nucleic Acids Res..

[13]  José M. López,et al.  Understanding MAPK Signaling Pathways in Apoptosis , 2020, International journal of molecular sciences.

[14]  L. Pasqualucci,et al.  Mutations in the RNA splicing factor SF3B1 promote tumorigenesis through MYC stabilization. , 2020, Cancer discovery.

[15]  S. Deaglio,et al.  Immune Response Dysfunction in Chronic Lymphocytic Leukemia: Dissecting Molecular Mechanisms and Microenvironmental Conditions , 2020, International journal of molecular sciences.

[16]  L. Bullinger,et al.  Prognostic and predictive role of gene mutations in chronic lymphocytic leukemia: results from the pivotal phase III study COMPLEMENT1. , 2020, Haematologica.

[17]  Dhanashree S. Kelkar,et al.  Hotspot SF3B1 mutations induce metabolic reprogramming and vulnerability to serine deprivation. , 2019, The Journal of clinical investigation.

[18]  Julio Delgado,et al.  The U1 spliceosomal RNA is recurrently mutated in multiple cancers , 2019, Nature.

[19]  J. Byrd,et al.  Efficacy of venetoclax in relapsed chronic lymphocytic leukemia is influenced by disease and response variables. , 2019, Blood.

[20]  J. Byrd,et al.  Long-term follow-up of the RESONATE phase 3 trial of ibrutinib vs ofatumumab. , 2019, Blood.

[21]  Angela N. Brooks,et al.  A Murine Model of Chronic Lymphocytic Leukemia Based on B Cell-Restricted Expression of Sf3b1 Mutation and Atm Deletion. , 2019, Cancer cell.

[22]  M. Warmuth,et al.  Sensitivity to splicing modulation of BCL2 family genes defines cancer therapeutic strategies for splicing modulators , 2019, Nature Communications.

[23]  Eun Woo Son,et al.  iDEP: an integrated web application for differential expression and pathway analysis of RNA-Seq data , 2018, BMC Bioinformatics.

[24]  S. Deaglio,et al.  The NOTCH Pathway and Its Mutations in Mature B Cell Malignancies , 2018, Front. Oncol..

[25]  G. Seelig,et al.  Degenerate minigene library analysis enables identification of altered branch point utilization by mutant splicing factor 3B1 (SF3B1) , 2018, Nucleic acids research.

[26]  Manoj M. Pillai,et al.  The Development and Use of Scalable Systems for Studying Aberrant Splicing in SF3B1-Mutant CLL. , 2018, Methods in molecular biology.

[27]  Angela N. Brooks,et al.  Splicing modulation sensitizes chronic lymphocytic leukemia cells to venetoclax by remodeling mitochondrial apoptotic dependencies. , 2018, JCI insight.

[28]  K. Neugebauer.  Faculty Opinions recommendation of Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins. , 2018, Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature.

[29]  B. Ebert,et al.  Synthetic Lethal and Convergent Biological Effects of Cancer-Associated Spliceosomal Gene Mutations. , 2018, Cancer cell.

[30]  K. de Heer,et al.  Clonal diversity predicts adverse outcome in chronic lymphocytic leukemia , 2018, Leukemia.

[31]  André Gohr,et al.  Matt: Unix tools for alternative splicing analysis , 2018, Bioinform..

[32]  P. A. Futreal,et al.  Clinical implications of cancer gene mutations in patients with chronic lymphocytic leukemia treated with lenalidomide. , 2018, Blood.

[33]  Ping Zhu,et al.  Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types. , 2018, Cell reports.

[34]  M. Warmuth,et al.  H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers , 2018, Nature Medicine.

[35]  J. Valcárcel,et al.  Molecular basis of differential 3′ splice site sensitivity to anti-tumor drugs targeting U2 snRNP , 2017, Nature Communications.

[36]  J. Valcárcel,et al.  Molecular basis of differential 3′ splice site sensitivity to anti-tumor drugs targeting U2 snRNP , 2017, Nature Communications.

[37]  B. Blencowe,et al.  An atlas of alternative splicing profiles and functional associations reveals new regulatory programs and genes that simultaneously express multiple major isoforms , 2017, Genome research.

[38]  M. Kashyap,et al.  A Challenging Pie to Splice: Drugging the Spliceosome. , 2017, Angewandte Chemie.

[39]  A. López-Guillermo,et al.  Clinical impact of the subclonal architecture and mutational complexity in chronic lymphocytic leukemia , 2017, Leukemia.

[40]  N. Barbosa-Morais,et al.  Alternative splicing: the pledge, the turn, and the prestige , 2017, Human Genetics.

[41]  R. Fulton,et al.  Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome , 2017, Nature Communications.

[42]  A. Hoskins,et al.  SF3b1 mutations associated with myelodysplastic syndromes alter the fidelity of branchsite selection in yeast , 2017, Nucleic acids research.

[43]  Susana Rodríguez-Santiago,et al.  SF3B1/Hsh155 HEAT motif mutations affect interaction with the spliceosomal ATPase Prp5, resulting in altered branch site selectivity in pre-mRNA splicing , 2016, Genes & development.

[44]  Jon C. Aster,et al.  Transcriptomic Characterization of SF3B1 Mutation Reveals Its Pleiotropic Effects in Chronic Lymphocytic Leukemia. , 2016, Cancer cell.

[45]  Henning Urlaub,et al.  Molecular Architecture of SF3b and Structural Consequences of Its Cancer-Related Mutations. , 2016, Molecular cell.

[46]  Michelle C. Chen,et al.  Physiologic Expression of Sf3b1(K700E) Causes Impaired Erythropoiesis, Aberrant Splicing, and Sensitivity to Therapeutic Spliceosome Modulation. , 2016, Cancer cell.

[47]  H. Varmus,et al.  Wild-Type U2AF1 Antagonizes the Splicing Program Characteristic of U2AF1-Mutant Tumors and Is Required for Cell Survival , 2016, bioRxiv.

[48]  Anil K. Kesarwani,et al.  Cancer associated SF3B1 mutants recognize otherwise inaccessible cryptic 3’ splice sites within RNA secondary structures , 2016, Oncogene.

[49]  Måns Magnusson,et al.  MultiQC: summarize analysis results for multiple tools and samples in a single report , 2016, Bioinform..

[50]  R. Kusec,et al.  Cryptic splicing events in the iron transporter ABCB7 and other key target genes in SF3B1-mutant myelodysplastic syndromes , 2016, Leukemia.

[51]  Marc Tessier-Lavigne,et al.  Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9 , 2016, Nature.

[52]  S. Armstrong,et al.  Modulation of splicing catalysis for therapeutic targeting of leukemias with spliceosomal mutations , 2016, Nature Medicine.

[53]  Jean-Paul Concordet,et al.  Improved Genome Editing Efficiency and Flexibility Using Modified Oligonucleotides with TALEN and CRISPR-Cas9 Nucleases. , 2016, Cell reports.

[54]  S. Roman-Roman,et al.  Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage , 2016, Nature Communications.

[55]  M. Larrayoz,et al.  The SF3B1 inhibitor spliceostatin A (SSA) elicits apoptosis in chronic lymphocytic leukaemia cells through downregulation of Mcl-1 , 2016, Leukemia.

[56]  Jacob E Corn,et al.  Enhancing homology-directed genome editing by catalytically active and inactive CRISPR-Cas9 using asymmetric donor DNA , 2016, Nature Biotechnology.

[57]  A. López-Guillermo,et al.  Clinical impact of clonal and subclonal TP53, SF3B1, BIRC3, NOTCH1, and ATM mutations in chronic lymphocytic leukemia. , 2015, Blood.

[58]  M. Warmuth,et al.  Cancer-Associated SF3B1 Hotspot Mutations Induce Cryptic 3' Splice Site Selection through Use of a Different Branch Point. , 2015, Cell reports.

[59]  Martin A. Nowak,et al.  Mutations driving CLL and their evolution in progression and relapse , 2015, Nature.

[60]  A. Valencia,et al.  Non-coding recurrent mutations in chronic lymphocytic leukaemia , 2015, Nature.

[61]  L. Rassenti,et al.  Targeting the spliceosome in chronic lymphocytic leukemia with the macrolides FD-895 and pladienolide-B , 2015, Haematologica.

[62]  E. Campo,et al.  The splicing modulator sudemycin induces a specific antitumor response and cooperates with ibrutinib in chronic lymphocytic leukemia , 2015, Oncotarget.

[63]  G. Ast,et al.  SF3B1 association with chromatin determines splicing outcomes. , 2015, Cell reports.

[64]  A. Derti,et al.  A chemical genetics approach for the functional assessment of novel cancer genes. , 2015, Cancer research.

[65]  Dennis Carson,et al.  Transcriptome Sequencing Reveals Potential Mechanism of Cryptic 3’ Splice Site Selection in SF3B1-mutated Cancers , 2015, PLoS Comput. Biol..

[66]  Robert J. Weatheritt,et al.  A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains , 2014, Cell.

[67]  W. Huber,et al.  Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 , 2014, Genome Biology.

[68]  H. Dvinge,et al.  Sample processing obscures cancer-specific alterations in leukemic transcriptomes , 2014, Proceedings of the National Academy of Sciences.

[69]  M. Howell,et al.  Functional genomics identifies a requirement of pre-mRNA splicing factors for sister chromatid cohesion , 2014, The EMBO journal.

[70]  E. Giné,et al.  A B-cell epigenetic signature defines three biologic subgroups of chronic lymphocytic leukemia with clinical impact , 2014, Leukemia.

[71]  E. Campo,et al.  Recurrent mutations refine prognosis in chronic lymphocytic leukemia , 2014, Leukemia.

[72]  S. Roman-Roman,et al.  A common alternative splicing signature is associated with SF3B1 mutations in malignancies from different cell lineages , 2014, Leukemia.

[73]  D. Rossi,et al.  Functional impact of NOTCH1 mutations in chronic lymphocytic leukemia , 2014, Leukemia.

[74]  Alfonso Valencia,et al.  Transcriptome characterization by RNA sequencing identifies a major molecular and clinical subdivision in chronic lymphocytic leukemia , 2014, Genome research.

[75]  David Gentien,et al.  SF3B1 mutations are associated with alternative splicing in uveal melanoma. , 2013, Cancer discovery.

[76]  F. J. Ramos,et al.  Phase I Pharmacokinetic and Pharmacodynamic Study of the First-in-Class Spliceosome Inhibitor E7107 in Patients with Advanced Solid Tumors , 2013, Clinical Cancer Research.

[77]  A. Hinnebusch,et al.  Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3 , 2013, Nature Genetics.

[78]  Catherine J. Wu,et al.  SF3B1 mutations in chronic lymphocytic leukemia. , 2013, Blood.

[79]  E. Campo,et al.  The genomic landscape of chronic lymphocytic leukemia: clinical implications , 2013, BMC Medicine.

[80]  E. Giné,et al.  NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome , 2013, Leukemia.

[81]  Yang Gao,et al.  Chemical perturbation of Mcl-1 pre-mRNA splicing to induce apoptosis in cancer cells. , 2013, ACS chemical biology.

[82]  A. Bowcock,et al.  Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma , 2013, Nature Genetics.

[83]  Thomas W. Owens,et al.  Dishevelled limits Notch signalling through inhibition of CSL , 2012, Development.

[84]  M. Cazzola,et al.  Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. , 2012, Blood.

[85]  A. McKenna,et al.  Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia , 2012, Cell.

[86]  J. Valcárcel,et al.  The spliceosome as a target of novel antitumour drugs , 2012, Nature Reviews Drug Discovery.

[87]  Schraga Schwartz,et al.  Differential GC content between exons and introns establishes distinct strategies of splice-site recognition. , 2012, Cell reports.

[88]  L. Pasqualucci,et al.  Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. , 2011, Blood.

[89]  E. Giné,et al.  Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia , 2011, Nature Genetics.

[90]  A. Sivachenko,et al.  SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. , 2011, The New England journal of medicine.

[91]  Peter J Campbell,et al.  Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms , 2011, Blood.

[92]  M. Stratton,et al.  Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. , 2011, The New England journal of medicine.

[93]  S. Sugano,et al.  Frequent pathway mutations of splicing machinery in myelodysplasia , 2011, Nature.

[94]  Juliane C. Dohm,et al.  Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia , 2011, Nature.

[95]  Christopher W. J. Smith,et al.  Genome-Wide Association between Branch Point Properties and Alternative Splicing , 2010, PLoS Comput. Biol..

[96]  C. Will,et al.  The Spliceosome: Design Principles of a Dynamic RNP Machine , 2009, Cell.

[97]  Michael Hiller,et al.  Widespread and subtle: alternative splicing at short-distance tandem sites. , 2008, Trends in genetics : TIG.

[98]  S. Akira,et al.  Essential function for the kinase TAK1 in innate and adaptive immune responses , 2005, Nature Immunology.

[99]  Christopher B. Burge,et al.  Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals , 2003, RECOMB '03.

[100]  K. Okkenhaug,et al.  PI3K in lymphocyte development, differentiation and activation , 2003, Nature Reviews Immunology.

[101]  Huitu Liu,et al.  MAPK signal pathways in the regulation of cell proliferation in mammalian cells , 2002, Cell Research.

[102]  J. Bae,et al.  MCL-1S, a Splicing Variant of the Antiapoptotic BCL-2 Family Member MCL-1, Encodes a Proapoptotic Protein Possessing Only the BH3 Domain* , 2000, The Journal of Biological Chemistry.

[103]  Y. S. Choi,et al.  Activation and proliferation of follicular dendritic cell-like cells by activated T lymphocytes. , 1994, Journal of immunology.

[104]  I. Higuchi,et al.  Control of Drosophila Sex-lethal pre-mRNA splicing by its own female-specific product. , 1992, Nucleic acids research.

[105]  A. Kohlmann,et al.  SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients , 2014, Leukemia.

[106]  P. LoRusso,et al.  A phase I, open-label, single-arm, dose-escalation study of E7107, a precursor messenger ribonucleic acid (pre-mRNA) splicesome inhibitor administered intravenously on days 1 and 8 every 21 days to patients with solid tumors , 2013, Investigational New Drugs.

[107]  R. Dalla‐Favera,et al.  Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia. , 2013, Blood.

[108]  Thomas R. Gingeras,et al.  STAR: ultrafast universal RNA-seq aligner , 2013, Bioinform..

[109]  E. Buratti,et al.  Exon and intron definition in pre‐mRNA splicing , 2013, Wiley interdisciplinary reviews. RNA.

[110]  P. Potter,et al.  The development and application of small molecule modulators of SF3b as therapeutic agents for cancer. , 2013, Drug discovery today.