News - SRSF2 mutation

Single cell long read genotyping of transcripts reveals discrete mechanisms of clonal evolution in post-MPN AML. (PubMed, Blood Adv)

In our analysis of post-MPN AMLs, we identified nine mutated loci across six genes (JAK2, IDH1/2, TP53, SRSF2, U2AF1) and linked these mutations to specific transcriptional phenotypes. Overall, LOTR-Seq provides novel insights into the evolution of post-MPN AML.

2 days ago

Journal • Tumor mutational burden • JAK2V617F

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • JAK2 (Janus kinase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

TP53 mutation • SRSF2 mutation

U2af1S34F and U2af1Q157R myeloid neoplasm-associated hotspot mutations induce distinct hematopoietic phenotypes in mice. (PubMed, Leukemia)

Collectively, our results support that U2AF1S34F and U2AF1Q157R mutations induce distinct hematopoietic, gene expression, and RNA splicing phenotypes in vivo. Larger population studies will be needed to determine if these phenotypic changes translate into clinico-pathologic differences in patients, warranting separate classification.

3 days ago

Preclinical • Journal

SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

SF3B1 mutation • SRSF2 mutation

Luspatercept for Anemia in Lower Risk MDS or Non-proliferative MDS/MPN Neoplasms (clinicaltrials.gov)

P2, N=6, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | N=70 --> 6

4 days ago

Enrollment closed • Enrollment change

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)

SF3B1 mutation • SRSF2 mutation

Reblozyl (luspatercept-aamt)

18d

The Clinicopathologic and Genomic Features of Mature Versus Blastic Plasmacytoid Dendritic Cell Neoplasms Arising From Chronic Myeloid Neoplasms. (PubMed, Am J Surg Pathol)

Our findings expand the histopathologic, immunophenotypic, and genetic characterization of MPDCP, and highlight pathologic features that distinguish it from BPDCN. Utilization of SOX4 immunohistochemistry, combined with careful clinical and molecular correlation, can aid in resolving these diagnostic challenges.

18 days ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD4 (CD4 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • CD5 (CD5 Molecule) • IRF8 (Interferon Regulatory Factor 8) • CD7 (CD7 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • SOX4 (SRY-Box Transcription Factor 4) • TCF4 (Transcription Factor 4)

RAS mutation • ASXL1 mutation • SRSF2 mutation

25d

Pre-diagnostic clonal hematopoiesis of indeterminate potential among patients with a primary cancer and risk of second cancers. (PubMed, Leukemia)

The risk for a second cancer was mainly observed in DNMT3A-, TET2-, SRSF2-, or JAK2-mutant CHIP. These findings suggest increased awareness of second cancer risk among patients with primary cancer and pre-diagnostic CHIP.

25 days ago

Journal

DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2)

TET2 mutation • SRSF2 mutation

Nonsense-Mediated RNA Decay is a Targetable Vulnerability in Splicing Factor Mutant Myeloid Neoplasms by Enhancing R-loop Accumulation and DNA Damage. (PubMed, Cancer Res)

Consequently, SMG1i-induced cell death in splicing factor mutant leukemias could be further enhanced by inhibition of ATR or RAD51. This study shows that in vivo targeting of NMD is a therapeutic strategy to treat myeloid neoplasms with aberrant splicing.

1 month ago

Journal

SRSF2 (Serine and arginine rich splicing factor 2) • RAD51 (RAD51 Homolog A)

SRSF2 mutation

Site-specific methylation of SRSF2P95H by SETD2 inhibits MDSC-mediated proinflammatory niche formation in mouse models of myelodysplastic syndrome. (PubMed, Sci Transl Med)

Mechanistically, SETD2 methylates SRSF2P95H at lysine-17 and lysine-65 to inhibit aberrant splicing of CEACAM1-4 (isoforms of carcinoembryonic antigen cell adhesion molecule), which enhances interleukin-1β (IL-1β) signaling through Slc7a11 (solute carrier family 7 member 11)-mediated cystine uptake, thereby promoting HSPC differentiation into MDSCs, establishing an IL-1β-driven immunosuppressive microenvironment. These findings identify the SRSF2P95HK17me1K65me2-CEACAM1-4 signaling axis as a promising therapeutic target in SRSF2P95-Mut MDS.

1 month ago

Preclinical • Journal

CEACAM5 (CEA Cell Adhesion Molecule 5) • SRSF2 (Serine and arginine rich splicing factor 2) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • SLC7A11 (Solute Carrier Family 7 Member 11) • CEACAM1 (CEA Cell Adhesion Molecule 1) • IL1B (Interleukin 1, beta)

SRSF2 mutation

BRAF Mutations in Myeloid Neoplasms: Prevalence, Co-Mutation Landscape, and Clinical Outcomes-A Comprehensive Review. (PubMed, Biomedicines)

BRAF mutations in myeloid neoplasms are rare, heterogeneous, and usually represent secondary events in clonal evolution. Although mutation clearance appears prognostically relevant, current targeted approaches provide limited durability, underscoring the need for prospective studies in this setting.

1 month ago

Clinical data • Review • Journal

BRAF (B-raf proto-oncogene) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2)

BRAF V600E • BRAF mutation • RAS mutation • ASXL1 mutation • SRSF2 mutation

2ms

LS1781: Ascorbic Acid and Chemotherapy for the Treatment of Relapsed or Refractory Lymphoma, CCUS, and Chronic Myelomonocytic Leukemia (clinicaltrials.gov)

P2, N=80, Recruiting, Mayo Clinic | Trial completion date: Mar 2027 --> Nov 2033 | Trial primary completion date: Mar 2027 --> Feb 2031

2 months ago

Trial completion date • Trial primary completion date

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • SF3B1 (Splicing Factor 3b Subunit 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CD4 (CD4 Molecule) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

IDH2 mutation • TET2 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation

cisplatin • carboplatin • gemcitabine • Rituxan (rituximab) • cytarabine • cyclophosphamide • ifosfamide • oxaliplatin • etoposide IV • decitabine • Truxima (rituximab-abbs) • Hemady (dexamethasone tablets) • Mabtas (rituximab biosimilar) • Starasid (cytarabine ocfosfate) • dexamethasone injection

2ms

GFH009X2101: Study of SLS009 (Formerly GFH009) a Potent Highly Selective CDK9 Inhibitor in Patients With Hematologic Malignancies and High-Risk Newly Diagnosed AML (clinicaltrials.gov)

P1/2, N=160, Recruiting, Sellas Life Sciences Group | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

2 months ago

Trial completion date • Trial primary completion date

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • DDX41 (DEAD-Box Helicase 41) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • KRAS mutation • FLT3-ITD mutation • Chr del(17p) • IDH1 mutation • IDH2 mutation • FLT3 mutation • TP53 wild-type • NPM1 mutation • KRAS wild-type • Chr del(11q) • ASXL1 mutation • SF3B1 mutation • EZH2 mutation • NRAS wild-type • SRSF2 mutation • IDH wild-type

Venclexta (venetoclax) • azacitidine • tambiciclib (SLS009)

2ms

Unlocking the undruggable spliceosome: generative AI and structural dynamics in cancer therapy. (PubMed, Front Cell Dev Biol)

Translating these mechanistic insights into the clinic, we evaluate the next-generation of therapeutic strategies, ranging from novel molecular biomarkers to rationally designed allosteric modulators and synthetic lethality. Finally, we discuss how deciphering these altered structural dynamics can guide the identification of splicing-derived neoantigens and biomarkers, establishing a roadmap for precision immunotherapy.

2 months ago

Review • Journal • IO biomarker

SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

SF3B1 mutation • SRSF2 mutation