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SF3B1 mutation
i
Other names: SF3B1, Splicing Factor 3b Subunit 1, Splicing Factor 3b Subunit 1 155kDa, Spliceosome-Associated Protein 155, Splicing Factor 3B Subunit 1, SF3b155, SAP155, Pre-MRNA Splicing Factor SF3b 155 KDa Subunit, Pre-MRNA-Splicing Factor SF3b 155 KDa Subunit, Splicing Factor 3b Subunit 1 155kD, Pre-MRNA Processing 10, SAP 155, Hsh155, PRPF10, PRP10, MDS
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Entrez ID:
5d
Classification and Prognostic Stratification Based on Genomic Features in Myelodysplastic and Myeloproliferative Neoplasm- and Their Overlapping Conditions. (PubMed, Cancers (Basel))
Improved survival was observed with transplantation in groups DP2, DP7, and DP9. These findings highlight the role of genomic classifications in guiding personalized treatment strategies, ultimately enhancing the understanding and management of myeloid neoplasms.
Journal
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TP53 (Tumor protein P53) • NPM1 (Nucleophosmin 1) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • SETBP1 (SET Binding Protein 1) • DDX41 (DEAD-Box Helicase 41) • CALR (Calreticulin)
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TP53 mutation • NPM1 mutation • SF3B1 mutation • DDX41 mutation • JAK2 mutation • SETBP1 mutation • CALR mutation
13d
New insights into the nature and classification of myelodysplastic neopmasm (PubMed, Zhonghua Yi Xue Za Zhi)
Morphological abnormalities include MDS with low blasts, MDS with increased blasts and hypoplastic MDS. This revision provides a foundation for precise diagnosis and treatment of MDS, further restricting the application of immunosuppressive therapy and advancing genetic research in diagnostics and therapeutics.
Journal
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TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1)
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TP53 mutation • SF3B1 mutation
14d
Luspatercept for Anemia in Lower Risk MDS or Non-proliferative MDS/MPN Neoplasms (clinicaltrials.gov)
P2, N=70, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Sep 2024 --> Jun 2025
Trial primary completion date
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SF3B1 (Splicing Factor 3b Subunit 1)
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SF3B1 mutation
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Reblozyl (luspatercept-aamt)
15d
Iron overload in acquired sideroblastic anemias and MDS: pathophysiology and role of chelation and luspatercept. (PubMed, Hematology Am Soc Hematol Educ Program)
Luspatercept, which can reduce SMAD2/SMAD3-dependent signaling implicated in suppression of erythropoiesis, may obviate the need for red blood cell transfusion in MDS-RS for more than a year, thereby diminishing further iron loading. However, luspatercept cannot be expected to substantially reduce the existing iron overload.
Review • Journal
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SF3B1 (Splicing Factor 3b Subunit 1) • ERFE (Erythroferrone) • SMAD3 (SMAD Family Member 3)
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SF3B1 mutation
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Reblozyl (luspatercept-aamt)
15d
SF3B1 Gene Mutations and Their Significance for Patients with Myelodysplastic Neoplasms (MDS) (ASH 2024)
Three are still alive and are undergoing azacitidine treatment at 6.5, 8.5, and 21 months after their diagnosis.Identification of splicing factor gene mutations is an important diagnostic tool for the stratification of MDS patients...Other biological factors such as the mutation variant, association with complex karyotypes, and mutations in other genes, may also affect the prognosis of patients with mutated SF3B1. Therefore, a comprehensive view that includes all cytogenomic, molecular, and clinical data is important for accurate diagnosis and personalized treatment of MDS patients.Supported by MH CZ-DRO 0064165
Clinical
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TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • BCORL1 (BCL6 Corepressor Like 1)
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TP53 mutation • NRAS mutation • TET2 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • Chr del(5q) • SF3B1 K666N • SF3B1 K700E
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Archer® VariantPlex® Myeloid panel
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azacitidine
16d
KRAS Variants Are Associated With Survival Outcomes and Genomic Alterations in Biliary Tract Cancers. (PubMed, JCO Precis Oncol)
The adverse impact of KRAS mutations in BTC is driven by G12 alterations in patients with IHC regardless of resection status, which was not observed in GB or EHC. There are unique comutational partners in distinct BTC subsets. These differences have important clinical implications in the era of KRAS-targeted therapeutics.
Journal
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KRAS (KRAS proto-oncogene GTPase) • SF3B1 (Splicing Factor 3b Subunit 1)
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KRAS mutation • KRAS G12D • KRAS wild-type • SF3B1 mutation • KRAS G12
18d
Perianal Paget Disease With an Enteric Phenotype and Associated In-Situ/Dysplastic Glandular Component: Report of a Potentially Novel Entity and Review of the Literature. (PubMed, Int J Surg Pathol)
Disease recurrence in this patient highlights the need for clinical vigilance. Defining the molecular profile in these lesions can also be useful, particularly when assessing potential treatment options for advanced disease.
Review • Journal
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1) • KRT7 (Keratin-7) • CDX2 (Caudal Type Homeobox 2) • KRT20 (Keratin 20)
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SF3B1 mutation
21d
Clinical Outcomes of Lung Transplant Recipients with Myelodysplastic Syndrome and Short Telomere Syndrome-Case Series. (PubMed, Transplant Proc)
Thus, abundance of caution is warranted when contemplating lung transplantation for individuals with high-risk MDS and STS. Further research is necessary to validate these findings.
Clinical data • Journal
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SF3B1 (Splicing Factor 3b Subunit 1)
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SF3B1 mutation
24d
Luspatercept for Anemia in Lower Risk MDS or Non-proliferative MDS/MPN Neoplasms (clinicaltrials.gov)
P2, N=70, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: May 2025 --> Sep 2025 | Trial primary completion date: May 2025 --> Sep 2024
Trial completion date • Trial primary completion date
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SF3B1 (Splicing Factor 3b Subunit 1)
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SF3B1 mutation
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Reblozyl (luspatercept-aamt)
24d
Cancer-associated SF3B1 mutation K700E causes widespread changes in U2/branchpoint recognition without altering splicing. (PubMed, bioRxiv)
These new BS are usually very close to the natural sites, occur upstream or downstream, and either exhibit stronger base-pairing potential with U2 snRNA or are adjacent to stronger polypyrimidine tracts than the WT sites. The widespread imprecision in BS recognition induced by K700E with limited changes in 3' ss selection supports a positive role for SUGP1 in early BS choice and expands the physiological consequences of this oncogenic mutation.
Journal
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SF3B1 (Splicing Factor 3b Subunit 1)
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SF3B1 mutation • SF3B1 K700E
27d
Alternative Splicing: A Potential Therapeutic Target in Hematological Malignancies. (PubMed, Hematol Rep)
Mutations in splicing factors, such as U2AF1, SF3B1, SRSF2, ZRSR2, and HNRNPH1, are frequently observed across various hematological malignancies and are associated with poor prognosis and treatment resistance. This research underscores the necessity of understanding the mechanisms of RNA splicing dysregulation in order to develop targeted therapies to correct these aberrant processes, thereby improving outcomes for patients with leukemia and related disorders.
Review • Journal
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SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • HNRNPH1 (Heterogeneous Nuclear Ribonucleoprotein H1)
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SF3B1 mutation • SRSF2 mutation • U2AF1 mutation
1m
RNA splicing as a therapeutic target in myelodysplastic syndromes. (PubMed, Semin Hematol)
Emerging evidence shows that splicing factor-mutant cells are more sensitive to perturbations targeting the spliceosome, aberrantly spliced genes and/or their regulated molecular pathways. This review summarizes current therapeutic strategies and ongoing efforts targeting splicing factor mutations for the treatment of MDS.
Journal
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SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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SF3B1 mutation • SRSF2 mutation • U2AF1 mutation
2ms
Development and Validation of a Biopsy-Free Scoring System for Screening Myelodysplastic Syndrome (MDS) and Associated Diseases in Cytopenic Patients (ASH 2024)
For patients with a probability score < 45%, a bone marrow study may not be needed, with a recommended follow-up every 6–12 months. This comprehensive analysis provides a useful and non-invasive predictive model that enhances diagnostic accuracy which potentially reduces unnecessary procedures.
Clinical • Biopsy
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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TP53 mutation • KRAS mutation • NRAS mutation • IDH2 mutation • NPM1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation
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Oncomine Myeloid Research Assay
2ms
Novel Plasma Cell-Free RNA-Based Liquid Biopsy Approach for CLL (ASH 2024)
Conclusions The presented liquid biopsy-based approach demonstrates the feasibility of identifying malignant cell fraction, BCR repertoires, clinically significant mutations, and immune and tissue specific processes from cfRNA. This study also suggests that the cfRNA platform may support longitudinal monitoring of CLL progression and relapse, as well the development of MRD tests with future validation.
Liquid biopsy • Biopsy
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TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • SF3B1 (Splicing Factor 3b Subunit 1) • BIRC3 (Baculoviral IAP repeat containing 3)
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TP53 mutation • ATM mutation • SF3B1 mutation • BIRC3 mutation
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BostonGene Tumor Portrait™ Test
2ms
Prognostic Role of NGS-Based MRD Assessment in FLT3-TKD Mutated Patients with Acute Myeloid Leukemia (ASH 2024)
Only two patients in the MRD negative group received the FLT3 inhibitor midostaurin combined with chemotherapy...NGS-MRD was not prognostic in this cohort of FLT3-TKD mutated AML patients. Shared first authors : Isabell Arnhardt, Christian M Vonk Shared senior authorship : Michael Heuser, Peter J.M. Valk
Clinical • Next-generation sequencing
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FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
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FLT3-ITD mutation • NPM1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • FLT3-TKD mutation
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TruSight Myeloid Sequencing Panel
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Rydapt (midostaurin)
2ms
Clonal Evolution of TP53 Configurations with Treatment Predict Prognosis in Myeloid Neoplasms (ASH 2024)
Such information will be invaluable for making treatment decisions in this grave prognostic disease otherwise. Ongoing work will dissect the exact treatment modalities and their influence on the TP53MT configurational switch.
TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
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TP53 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation
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TruSight Myeloid Sequencing Panel
2ms
CORONADO CLL: RP-3500 and Olaparib in DNA Damage Repair Pathway Deficient Relapsed/Refractory Chronic Lymphocytic Leukemia (clinicaltrials.gov)
P1/2, N=5, Terminated, University of Utah | N=39 --> 5 | Trial completion date: Aug 2027 --> Oct 2024 | Recruiting --> Terminated; This study was terminated due to sponsor de-activation of all programs associated with RP-3500 (camonsertib).
Enrollment change • Trial completion date • Trial termination
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TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • SF3B1 (Splicing Factor 3b Subunit 1) • CCND1 (Cyclin D1) • CD5 (CD5 Molecule) • POT1 (Protection of telomeres 1) • FCER2 (Fc Fragment Of IgE Receptor II)
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TP53 mutation • ATM mutation • Chr t(11;14) • SF3B1 mutation
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Lynparza (olaparib) • camonsertib (RP-3500)
2ms
A Complete Response to Combined Immunotherapy in a Patient with an ATM plus SF3B1 Mutation and a Moderate Tumor Mutational Burden with a High-Grade Treatment-Emergent Neuroendocrine Prostate Cancer: Case Report and Review of the Literature. (PubMed, Case Rep Oncol)
We describe an impressive response to IO combination immunotherapy with ipilimumab plus nivolumab (Ipi/nivo) in a patient with T-NEPC who had failed standard treatment approaches. The results of the next-generation sequencing DNA analysis demonstrated the presence of intermediary tumor burden, an ATM mutation and a rare SF3B1 (G742D) mutation, and served as rational for IO therapy in this patient. This case highlights the genetic profile of tumor with a rare combination of ATM and SF3B1 mutations that could be further explored as biomarkers for IO therapy in T-NEPC and other tumor types.
Review • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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TMB (Tumor Mutational Burden) • ATM (ATM serine/threonine kinase) • SF3B1 (Splicing Factor 3b Subunit 1)
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ATM mutation • SF3B1 mutation
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Opdivo (nivolumab) • Yervoy (ipilimumab)
2ms
Prognostic impact of next-generation sequencing on myelodysplastic syndrome: A single-center experience. (PubMed, Medicine (Baltimore))
According to early findings, NGS panels are extremely effective instruments that provide an entirely new viewpoint on the disease for particular individuals. Future prognostications will depend more on NGS because those who exhibit normal cytogenetics may additionally have gene mutations.
Journal • Next-generation sequencing
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TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • SRSF2 (Serine and arginine rich splicing factor 2) • CSF3R (Colony Stimulating Factor 3 Receptor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • SETBP1 (SET Binding Protein 1) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • PHF6 (PHD Finger Protein 6)
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ASXL1 mutation • TET2 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • PHF6 mutation
2ms
Future directions in myelodysplastic syndromes/neoplasms and acute myeloid leukaemia classification: from blast counts to biology. (PubMed, Histopathology)
Going forward, the application of machine learning and advanced statistical methods to large patient cohorts can refine future classifications by advancing unbiased and robust previously unrecognised disease subgroups. Future classifications will probably incorporate these newer technologies and higher-level analyses that emphasise genomic disease entities over traditional morphologically defined entities, thus promoting more accurate diagnosis and patient risk stratification.
Review • Journal
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TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1)
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TP53 mutation • SF3B1 mutation
2ms
Experience with luspatercept therapy in patients with transfusion-dependent low-risk myelodysplastic syndromes in real-world clinical practice: exploring the positive effect of combination with erythropoietin alfa. (PubMed, Front Oncol)
Epoetin alfa was used simultaneously in 31 patients (60.7%). The effect was particularly high in the IPSS-M low and very low groups. We believe that the relatively high response rate in our patients was influenced by the frequent use of a higher dose (1.75 mg/kg) and especially by adding ESA to luspatercept in poorly responding patients.
Journal • Real-world evidence • Real-world
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SF3B1 (Splicing Factor 3b Subunit 1) • TGFB1 (Transforming Growth Factor Beta 1)
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SF3B1 mutation
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Reblozyl (luspatercept-aamt)
2ms
Hyperactivation of NF-κB signaling in splicing factor mutant myelodysplastic syndromes and therapeutic approaches. (PubMed, Adv Biol Regul)
The potent IRAK4 inhibitor CA-4948 has shown efficacy in both pre-clinical studies and MDS clinical trials, with splicing factor mutant patients showing the higher response rates. Emerging data has, however, revealed that co-targeting of IRAK4 and its paralog IRAK1 is required to maximally suppress LSPC function in vitro and in vivo by inducing cellular differentiation. These findings provide a link between the presence of the commonly mutated splicing factor genes and activation of innate immune signaling pathways in myeloid malignancies and have important implications for targeted therapy in these disorders.
Journal
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SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)
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SF3B1 mutation • SRSF2 mutation • U2AF1 mutation
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emavusertib (CA-4948)
2ms
Therapeutic strategies targeting aberrant RNA splicing in myeloid malignancies. (PubMed, Br J Haematol)
Mutations in spliceosomal components have been identified in numerous cancer subtypes, with mutations in RNA binding proteins SF3B1, SRSF2, U2AF1, and ZRSR2 occurring frequently in AML and in up to 60% of patients with MDS, as well as in chronic myelomonocytic leukaemia and in 10% of patients with chronic lymphocytic leukaemia. In this review, we explore therapeutic strategies targeting aberrant splicing and the potential of these approaches to drive clinical responses.
Review • Journal
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SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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SF3B1 mutation • SRSF2 mutation • U2AF1 mutation
3ms
The Impact of Spliceosome Inhibition in SF3B1-Mutated Uveal Melanoma. (PubMed, Invest Ophthalmol Vis Sci)
Moreover, E7107 had the greatest effect on intron retention. This study indicates/suggests that mutated SF3B1 UM cells are more sensitive to the splicing inhibitor E7107 than wild-type SF3B1 UM cells.
Journal
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SF3B1 (Splicing Factor 3b Subunit 1) • BAP1 (BRCA1 Associated Protein 1) • CASP3 (Caspase 3)
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SF3B1 mutation • BAP1 mutation
3ms
Uveal Melanoma: Molecular and Genetic Mechanisms of Development and Therapeutic Approaches (PubMed, Mol Biol (Mosk))
New drugs undergoing clinical trials are mostly targeted drugs designed to inhibit the protein products of mutant genes or immunotherapeutic agents designed to stimulate the immune response against specific antigens. In addition to these approaches, potential therapeutic targets of epigenetic regulation of UM development are considered in the review.
Review • Journal • IO biomarker
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GNAQ (G Protein Subunit Alpha Q) • SF3B1 (Splicing Factor 3b Subunit 1) • BAP1 (BRCA1 Associated Protein 1) • GNA11 (G Protein Subunit Alpha 11) • EIF1AX (Eukaryotic Translation Initiation Factor 1A X-Linked)
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GNAQ mutation • SF3B1 mutation • BAP1 mutation
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Kimmtrak (tebentafusp-tebn)
3ms
Cancer-associated SF3B1-K700E mutation controls immune responses by regulating Treg function via aberrant Anapc13 splicing. (PubMed, Sci Adv)
In addition, acute myeloid leukemia grows faster in aged, but not young, Sf3b1K700Efl/+/Foxp3YFP-Cre mice compared to Foxp3YFP-Cre mice. Our results highlight the impact of cancer-associated SF3B1 mutation on immune responses, which affect cancer development.
Journal
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SF3B1 (Splicing Factor 3b Subunit 1) • CD4 (CD4 Molecule)
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SF3B1 mutation • SF3B1 K700E • FOXP3 expression
3ms
Ibrutinib, Fludarabine, and Pembrolizumab in High-Risk or Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (clinicaltrials.gov)
P2, N=15, Active, not recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Dec 2026 --> Dec 2025
Trial completion date • IO biomarker
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TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1)
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TP53 mutation • NOTCH1 mutation • SF3B1 mutation
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Keytruda (pembrolizumab) • Imbruvica (ibrutinib) • fludarabine IV
3ms
Prognostic impact of DTA mutation and co-occurring mutations in patients with myelodysplastic syndrome. (PubMed, Mol Biol Rep)
DTA mutations are frequently observed in patients with MDS, often accompanied by genes involved in RNA splicing and transcription factors like SF3B1 and RUNX1. DTA and concomitant mutations affect prognosis in MDS patients and RUNX1 was identified as an independent poor prognostic factor in patients with DTA mutations.
Retrospective data • Journal
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TP53 (Tumor protein P53) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1)
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TP53 mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • U2AF1 mutation
3ms
Long-read transcriptome sequencing of CLL and MDS patients uncovers molecular effects of SF3B1 mutations. (PubMed, Genome Res)
Using transcriptome-wide RNA binding maps and molecular dynamics simulations, we showed multimodal SF3B1 binding at 3' splice sites and predicted reduced RNA binding at the second binding pocket of SF3B1K700E Our work presents the hitherto most complete LRTS study of the SF3B1 mutation in CLL and MDS and provides a resource to study aberrant splicing in cancer. Moreover, we showed that different disease prognosis most likely results from the different cell types expanded during carcinogenesis rather than different mechanisms of action of the mutated SF3B1 These results have important implications for understanding the role of SF3B1 mutations in hematological malignancies and other related diseases.
Journal
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SF3B1 (Splicing Factor 3b Subunit 1)
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SF3B1 mutation • SF3B1 K700E
3ms
Presence of triple positive driver mutations in JAK2, CALR and MPL in primary myelofibrosis: a case report and literature review. (PubMed, Hematology)
The patient was diagnosed with PMF and treated with ruxolitinib and COPD therapy...The rare coexistence of JAK2, CALR, and MPL mutations challenges the assumption of their mutual exclusivity. Further study of these mutations is essential for developing better treatment strategies.
Review • Journal
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JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • STAG2 (Stromal Antigen 2) • CALR (Calreticulin)
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ASXL1 mutation • SF3B1 mutation • SRSF2 mutation • STAG2 mutation • JAK2 mutation
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Jakafi (ruxolitinib)
3ms
The non-canonical BAF chromatin remodeling complex is a novel target of spliceosome dysregulation in SF3B1-mutated chronic lymphocytic leukemia. (PubMed, Leukemia)
Finally, Cancer Dependency Map analysis and BRD9 inhibition displayed BRD9 dependency and sensitivity in cell lines and primary CLL cells. In conclusion, spliceosome dysregulation caused by SF3B1 mutations leads to multiple ASEs and an altered ncBAF complex interactome, highlighting a novel pathobiological mechanism in SF3B1MUT CLL.
Journal • BRCA Biomarker
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BRCA2 (Breast cancer 2, early onset) • SF3B1 (Splicing Factor 3b Subunit 1)
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SF3B1 mutation • SF3B1 K700E
3ms
Cancer-associated SF3B1 Mutations Inhibit mRNA Nuclear Export by Disrupting SF3B1-THOC5 Interactions. (PubMed, J Biochem)
Importantly, other types of cancer-associated SF3B1 mutations also inhibited mRNA nuclear export similarly, suggesting that it is common for cancer-associated SF3B1 mutation to inhibit mRNA nuclear export. Our research highlights the critical role of the THOC5-SF3B1 interaction in the regulation of mRNA nuclear export and provides valuable insights into the impact of SF3B1 mutations on mRNA nuclear export.
Journal
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SF3B1 (Splicing Factor 3b Subunit 1)
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SF3B1 mutation • SF3B1 K700E
3ms
Genomic landscape of cutaneous, acral, mucosal, and uveal melanoma in Japan: analysis of clinical comprehensive genomic profiling data. (PubMed, Int J Clin Oncol)
The distinct genomic profiling in Japanese patients, including lower TMB, compared to Caucasians, is associated with poorer treatment outcomes. This result underscores the need for more effective therapeutic agents.
Journal • Tumor mutational burden • MSi-H Biomarker • IO biomarker
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BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • GNAQ (G Protein Subunit Alpha Q) • SF3B1 (Splicing Factor 3b Subunit 1) • CCND1 (Cyclin D1) • BAP1 (BRCA1 Associated Protein 1) • GNA11 (G Protein Subunit Alpha 11) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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BRAF V600E • MSI-H/dMMR • NRAS mutation • BRAF V600 • BRAF V600K • NF1 mutation • SF3B1 mutation • GNA11 mutation • BAP1 mutation • NRAS G13
7ms
Myelodysplastic Syndrome Related to Successful Treatment With177Lu-PSMA for Metastatic Castration-Refractory Prostate Cancer. (PubMed, Clin Nucl Med)
177Lu-vipivotide tetraxetan (177Lu-PSMA-617/LuPSMA) received recent EMA approval for metastatic castration-resistant prostate cancer, with promising data for earlier stages...We present a 77-year-old man, with synchronous liver, bone, and lymph node metastatic prostate cancer, having developed a low-risk MDS with SF3B1 mutation, 1 month after the sixth administration of LuPSMA. Although on partial metabolic and biological response with PSA nadir at 7 months after therapy, life quality was significantly altered by MDS.
Journal • Metastases
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SF3B1 (Splicing Factor 3b Subunit 1)
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SF3B1 mutation
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Pluvicto (lutetium Lu 177 vipivotide tetraxetan)
7ms
(G)Patching up mis-splicing in cancer. (PubMed, Trends Biochem Sci)
GPATCH8 cooperates with SF3B1 mutants, affecting the splicing machinery. Targeting GPATCH8 reveals therapeutic opportunities for SF3B1 mutant cancers and other splicing-related diseases.
Journal
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SF3B1 (Splicing Factor 3b Subunit 1)
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SF3B1 mutation
7ms
Biological relevance of alternative splicing in hematologic malignancies. (PubMed, Mol Med)
In this review, we discuss aberrant splicing events induced by mutations affecting SFs (SF3B1, U2AF1, SRSR2, and ZRSR2), spliceosome components (PRPF8, LUC7L2, DDX41, and HNRNPH1), and epigenetic modulators (IDH1 and IDH2). Finally, we provide an extensive overview of the biological relevance of aberrant isoforms of genes involved in the regulation of apoptosis (e. g. BCL-X, MCL-1, FAS, and c-FLIP), activation of key cellular signaling pathways (CASP8, MAP3K7, and NOTCH2), and cell metabolism (PKM).
Review • Journal
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • SF3B1 (Splicing Factor 3b Subunit 1) • BCL2L1 (BCL2-like 1) • NOTCH2 (Notch 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • DDX41 (DEAD-Box Helicase 41) • CASP8 (Caspase 8) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • HNRNPH1 (Heterogeneous Nuclear Ribonucleoprotein H1) • MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7) • PRPF8 (Pre-MRNA Processing Factor 8)
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SF3B1 mutation • U2AF1 mutation
7ms
The E592K variant of SF3B1 creates unique RNA missplicing and associates with high-risk MDS without ring sideroblasts. (PubMed, Blood Adv)
Moreover, compared to other hotspot SF3B1 mutations, E592K induces a unique RNA missplicing pattern, retains an interaction with the splicing factor SUGP1, and preserves normal RNA splicing of the sideroblastic anemia genes TMEM14C and ABCB7. These data have implications for our understanding of the functional diversity of spliceosome mutations, as well as the pathobiology, classification, prognosis, and management of SF3B1-mutant MDS.
Journal
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SF3B1 (Splicing Factor 3b Subunit 1)
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SF3B1 mutation
7ms
RET Alterations Differentiate Molecular Profile of Medullary Thyroid Cancer. (PubMed, JCO Precis Oncol)
Altogether, this study provides a detailed genomic characterization of patients with MTC of Indian origin, highlighting the possible utility of targeted therapies in this disease.
Journal
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • RET (Ret Proto-Oncogene) • HRAS (Harvey rat sarcoma viral oncogene homolog) • SF3B1 (Splicing Factor 3b Subunit 1)
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KRAS mutation • BRAF mutation • RET mutation • SF3B1 mutation
7ms
COMBINED PIRTOBRUTINIB, VENETOCLAX, AND OBINUTUZUMAB IN FIRST-LINE TREATMENT OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): A PHASE 2 TRIAL (EHA 2024)
Background: Treatment with combined covalent BTK-inhibitor (cBTKi such as ibrutinib, acalabrutinib, zanubrutinib) withBCL2-inhibitor, venetoclax +/- CD20 monoclonal antibody obinutuzumab showed high rates of undetectableMRD (U-MRD) remission in patients (pts) with CLL (Jain, NEJM 2019; Munir NEJM 2023; Wierda, JCO 2021; Kater, NEJM Evidence 2022). We report the first results for first-line combined pirtobrutinib, venetoclax, and obinutuzumab in pts with CLL. Avery high rate of bone marrow U-MRD at 10-6 sensitivity was noted at 6-months of combined treatment. Adverse event profile was similar to what was noted in previous studies with these agents.
P2 data • Clinical
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TP53 (Tumor protein P53)
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TP53 mutation • KRAS mutation • NOTCH1 mutation • Chr del(11q) • SF3B1 mutation • TP53 mutation + Chr del(17p) • Chr del(17p) + Chr del(11q) • TS 12
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clonoSEQ
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Venclexta (venetoclax) • Imbruvica (ibrutinib) • Gazyva (obinutuzumab) • Brukinsa (zanubrutinib) • Calquence (acalabrutinib) • Jaypirca (pirtobrutinib)
8ms
Predicting survival in patients with myelodysplastic/myeloproliferative neoplasms with SF3B1 mutation and thrombocytosis. (PubMed, Leukemia)
According to the univariable analyses of OS, age ≥ 65 years (P < 0.001), hemoglobin concentration (Hb) < 80 g/L (P = 0.090), platelet count (PLT) ≥ 800 × 10E + 9/L (P = 0.087), bone marrow RS < 15% (P < 0.001), the Revised International Prognostic Scoring System (IPSS-R) cytogenetic category intermediate/poor/very poor (P = 0.005), SETBP1 mutation (P = 0.061) and SRSF2 mutation (P < 0.001) were associated with poor survival. Based on variables selected from univariable analyses, two separate survival prediction models, a clinical survival model, and a clinical-molecular survival model, were developed using multivariable analyses with the minimum value of the Akaike information criterion (AIC) to specifically predict outcomes in patients with MDS/MPN-SF3B1-T according to the 2022 WHO classification.
Journal
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SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2) • SETBP1 (SET Binding Protein 1)
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SF3B1 mutation • SRSF2 mutation • SETBP1 mutation
8ms
The Identification of an Activating ESR1 Mutation in an Aggressive Prolactinoma Enabled the Use of Personalized Treatment (ENDO 2024)
Elacestrant, a second-line ER degrader, increases overall free-survival in patients with resistant breast cancer and ESR1Y537S...Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.
ER (Estrogen receptor) • SF3B1 (Splicing Factor 3b Subunit 1) • MEN1 (Menin 1)
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ER positive • ER mutation • ER Y537S • SF3B1 mutation • ESR1 mutation
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OncoPanel™ Assay
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Orserdu (elacestrant)
8ms
GPATCH8 modulates mutant SF3B1 mis-splicing and pathogenicity in hematologic malignancies. (PubMed, Mol Cell)
Silencing of GPATCH8 corrected one-third of mutant SF3B1-dependent splicing defects and was sufficient to improve dysfunctional hematopoiesis in SF3B1-mutant mice and primary human progenitors. These data identify GPATCH8 as a novel splicing factor required for mis-splicing by mutant SF3B1 and highlight the therapeutic impact of correcting aberrant splicing in SF3B1-mutant cancers.
Journal
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SF3B1 (Splicing Factor 3b Subunit 1)
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SF3B1 mutation
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