News - SRSF2 mutation

Targeting EZH2 Oncogenic Splicing: Decoding the Regulatory Network and Antisense Correction. (PubMed, bioRxiv)

Our lead ASO successfully corrects aberrant splicing and NMD, restores the expression and function of EZH2, and partially rescues hematopoietic defects and cellular properties. Our study demonstrates that ASO pharmacology is an actionable strategy for clinical development, challenging the existing paradigms in SF-mutated cancers.

6 days ago

Journal

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • SRSF2 (Serine and arginine rich splicing factor 2)

SRSF2 mutation

PU.1-Activated Genomic Regions Define Low-risk MDS Subsets Characterized by Immune Dysregulation and Disease Progression. (PubMed, Blood)

Functional studies demonstrate that PU.1 inhibition suppresses MDS cell proliferation and clonogenicity, as impaired PU.1 binding inhibits the activation of key transcriptional programs involved in disease advancement. Collectively, these findings identify epigenetic factors that predispose low-risk MDS patients to progression into high-risk MDS and, ultimately, sAML.

7 days ago

Journal

SRSF2 (Serine and arginine rich splicing factor 2) • CD34 (CD34 molecule)

SRSF2 mutation

MDS/AML and AML with myelodysplasia-related gene mutations: clinical and molecular similarities. (PubMed, Blood Adv)

MRD of secondary type mutations alone lacks predictive value, yet MRD of non-DTA mutations in CR is associated with increased CIR in st-AML (SHR MRDpos vs. MRDneg 3.25; p<0.001). Molecularly-defined st-AML, including st-MDS/AML, defines a distinct AML category with a unique genetic, clinical and treatment response profile, in which NGS-based MRD holds markedly prognostic significance.

9 days ago

Journal

SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • ETV6 (ETS Variant Transcription Factor 6) • 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)

ASXL1 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation

10d

A Yeast-Based High-Throughput Screening Platform for the Discovery of Novel pre-mRNA Splicing Modulators. (PubMed, ACS Chem Biol)

Transcriptome analyses showed that this compound causes widespread changes in gene expression in sensitive SRSF2P95H-expressing cells. Our results demonstrate the utility of using a yeast-based HTS to identify compounds capable of changing pre-mRNA splicing outcomes.

10 days ago

Journal

SRSF2 (Serine and arginine rich splicing factor 2)

SRSF2 mutation

13d

CEBPA-bZIP Mutations in AML Patients Treated With Non-Intensive Therapy: A Study by the Spanish PETHEMA Registry. (PubMed, Hematol Oncol)

We concluded that our series of non-IT AML patients within the PETHEMA registry confirm a low percentage of CEBPA mutated cases which are frequently co-mutated with MDS related genes. Those CEBPA-bZIP cases harbor a similar median OS than those belonging to favorable ELN2024 risk category.

13 days ago

Journal

TP53 (Tumor protein P53) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

TP53 mutation • SRSF2 mutation

20d

Synergistic intragenic epigenetic deregulation by IDH2 and SRSF2 mutations causes mis-splicing of key transcriptional regulators. (PubMed, Sci Adv)

Instead, the mis-spliced genes encode for proteins that interact with the complexes regulating these differentially expressed genes. Thus, aberrant DNAme and splicing lead to the mis-splicing of key regulatory complexes, resulting in the aberrant gene expression profiles characteristic of these AMLs.

20 days ago

Journal

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • SRSF2 (Serine and arginine rich splicing factor 2)

SRSF2 mutation

Correlates of organ damage in patients with advanced systemic mastocytosis enrolled in clinical trials of avapritinib. (PubMed, Blood Neoplasia)

Notably, 47% of patients received previous midostaurin. AdvSM subtype, the presence and number of additional comutated genes beyond KIT D816V, BM mast cell burden, and KIT D816V variant allele fraction were associated with the presence and/or number of WHO/mIWG organ damage findings. Our study provides a snapshot of the correlates of organ damage in patients enrolled in clinical trials of avapritinib and identifies a key association between molecular profile and burden of organ damage.

1 month ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2)

RUNX1 mutation • ASXL1 mutation • SRSF2 mutation

midostaurin • Ayvakit (avapritinib)

CSF3R Mutations Imply Adverse Prognostic Impact in Adult Acute Myeloid Leukemia Patients: A Single-Center Retrospective Study. (PubMed, Cancer Med)

CSF3R mutations define a distinct, high-risk AML subset characterized by an inferior treatment response and survival, warranting incorporation into future risk stratification.

1 month ago

Retrospective data • Journal

NPM1 (Nucleophosmin 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • CSF3R (Colony Stimulating Factor 3 Receptor) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

NPM1 mutation • ASXL1 mutation • EZH2 mutation • SRSF2 mutation

ALLO-BAT: Study of Stem Cell Transplant vs. Non-Transplant Therapies in High-Risk Myelofibrosis (clinicaltrials.gov)

P=N/A, N=90, Recruiting, University Health Network, Toronto | Trial completion date: Feb 2026 --> Dec 2026 | Trial primary completion date: Aug 2025 --> Dec 2026

1 month ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CALR (Calreticulin)

TP53 mutation • ASXL1 mutation • EZH2 mutation • SRSF2 mutation • CALR mutation

Jakafi (ruxolitinib) • hydroxyurea

Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)

P1, N=32, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

1 month ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DEK (DEK Proto-Oncogene) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • EZH2 mutation • SRSF2 mutation • Chr del(5q)

cytarabine • Pemazyre (pemigatinib) • daunorubicin • Starasid (cytarabine ocfosfate)

Integration of genomic and clinical variables improves the prediction of myelodysplastic syndromes to acute myeloid leukaemia transformation and prognosis. (PubMed, Br J Haematol)

This work provides the first genomic characterisation of a diagnosed MDS cohort in China and establishes the first risk prediction model for MDS-to-AML transformation, alongside novel prognostic models for OS and PFS. These tools offer improved prognostic prediction and potential guidance for therapeutic strategies in Chinese patients with MDS.

1 month ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • CSF3R (Colony Stimulating Factor 3 Receptor) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • GATA2 (GATA Binding Protein 2) • CALR (Calreticulin)

TP53 mutation • SRSF2 mutation • STAT3 mutation

Atypical chronic myeloid leukemia: From diagnosis to molecular features and therapeutic options. (PubMed, Hemasphere)

The most used agents include hydroxyurea, interferon, hypomethylating agents, and JAK inhibitors, although none of them are disease-modifying. Allogeneic hematopoietic stem cell transplant remains the only potentially curative approach and should be considered in all eligible patients. Actionable mutations (CSF3R, NRAS/KRAS, and KIT) have also been identified, supporting the development of new agents targeting the involved pathways.

1 month ago

Review • Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CSF3R (Colony Stimulating Factor 3 Receptor) • SETBP1 (SET Binding Protein 1) • ETNK1 (Ethanolamine Kinase 1)

KRAS mutation • NRAS mutation • KIT mutation • ASXL1 mutation • TET2 mutation • EZH2 mutation • CBL mutation • SRSF2 mutation

hydroxyurea