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BIOMARKER:

SF3B1 K666N

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
Entrez ID:
Related biomarkers:
5ms
Altered RNA Export in SF3B1 Mutants Increases Sensitivity to Nuclear Export Inhibition (ASH 2023)
Previous findings from a phase 2 clinical trial of the XPO1 inhibitor selinexor in patients with high-risk myelodysplastic syndrome (MDS) relapsed or refractory to hypomethylating agents (HMA) revealed increased activity in patients with SF3B1 mutations...Using the Bliss independence model to calculate synergy, we identifed two drugs that greatly synergized with eltanexor specifically in the SF3B1 mutant cell lines: venetoclax (a BCL2 inhibitor), and navitoclax (a BCL2/BCL-XL inhibitor)...Our findings may also contribute to the development of potentially synergistic therapeutic combinations. In this regard, recent human data have shown that venetoclax can overcome the poor prognosis of spliceosomal mutant AML patients (Senapati et al, Blood 2023); therefore, combining eltanexor with venetoclax could represent a promising SF3B1-specific therapy.
IO biomarker
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SF3B1 (Splicing Factor 3b Subunit 1) • BCL2L1 (BCL2-like 1) • XPO1 (Exportin 1) • SIK1 (Salt Inducible Kinase 1)
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SF3B1 mutation • SF3B1 K666N • SF3B1 K700E • XPO1 mutation
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Venclexta (venetoclax) • Xpovio (selinexor) • navitoclax (ABT 263) • eltanexor (KPT-8602)
11ms
EXPLORING CLONAL COMPETITION THROUGH 12-YEAR FOLLOW-UP OF AN MDS-RS PATIENT WITH DUAL SF3B1 MUTATIONS (EHA 2023)
We identified mutation-specific splicing profiles and intricate patterns of tumor suppressor gene expression as potential compound factors to the varied clonal fitness of SF3B1 mutations. This unique patient enabled the identification and tracking of mechanisms underlying long-term clonal expansion and competition, which we aim to verify in further work. Hematopoiesis, Myelodysplastic syndrome, Myelodysplasia, RNA-seq
Clinical
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SF3B1 (Splicing Factor 3b Subunit 1) • CD34 (CD34 molecule)
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SF3B1 mutation • SF3B1 K666N
over1year
Long-Term Clonal Inversion in an MDS-RS Case with Dual SF3B1 Mutations (ASH 2022)
In conclusion, this case study comprises a unique long-term follow-up of the clonal dynamics underlying two co-existing, distinct and competing SF3B1mt clones which identifies subtle molecular changes and differences underlying the expansion and progression of SF3B1mt clones. *Moura PL, Hofman IJF, Nannya Y and Aliouat A contributed equally to this work.
Clinical
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SF3B1 (Splicing Factor 3b Subunit 1) • CD34 (CD34 molecule) • SEPTIN6 (Septin 6) • MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7)
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SF3B1 mutation • SF3B1 K666N
3years
[VIRTUAL] Inhibiting the nuclear exporter XPO1 and the antiapoptotic factor BCL2 is synergistic in XPO1 and SF3B1 mutant hematologic malignancies (AACR 2021)
We therefore hypothesized that combining selinexor and venetoclax would have potential synergy and could be used to target hematologic malignancies bearing XPO1 and SF3B1 mutations.We first determined whether XPO1 and SF3B1 mutant cell lines showed differential response to either selinexor or venetoclax monotherapy. This combination is highly promising as an all oral regimen for hematologic malignancies bearing these mutations. Further, preclinical testing in in vivo using XPO1 and SF3B1 mutant and wildtype mice is ongoing.
IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • SF3B1 (Splicing Factor 3b Subunit 1) • MCL1 (Myeloid cell leukemia 1) • XPO1 (Exportin 1) • RELA (RELA Proto-Oncogene)
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SF3B1 mutation • SF3B1 K666N • XPO1 E571K • XPO1 mutation
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Venclexta (venetoclax) • Xpovio (selinexor)
over3years
[VIRTUAL] Molecular and Clinical Aspects of Acute Myeloid Leukemia with Inv(3)(q21q26)/t(3;3)(q21;q26) Carrying Spliceosomal Mutations (ASH 2020)
1. In sum, we describe that SF3B1 mutations occur in combination with inv(3)/t(3;3) in AML and might represent a subclass of this entity in which lesions in SF3B1 gene could potentially hide a cryptic association between splicing abnormalities and disease phenotypes.
Clinical
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NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • CBL (Cbl proto-oncogene) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • GATA2 (GATA Binding Protein 2)
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NRAS mutation • DNMT3A mutation • NF1 mutation • ASXL1 mutation • SF3B1 mutation • CBL mutation • U2AF1 mutation • Chr del(5q) • SF3B1 K666N • SF3B1 K700E • GATA2 mutation