News - SRSF2 mutation

Splicing factor mutations clearance and outcomes in clonal myeloid neoplasms: a referral center experience. (PubMed, Ann Hematol)

Median OS was 27.2 vs. 17.2 months in AML and 16.7 vs. 23.7 months in MDS/CMML for clearance versus persistence groups, respectively. These findings suggest that SF mutation clearance does not significantly impact OS but may influence other clinical outcomes in patients with myeloid neoplasms harboring SF mutations.

4 days ago

Journal

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

Mutational Landscape and Clinical Outcomes in AML With Sole Trisomy 8. (PubMed, Hematol Oncol)

Categorizing patients on the basis of MR gene mutations revealed that the inferior survival of sole +8 patients may be attributed to the high frequency of MR gene mutations in these patients. These findings indicate the importance of genetic mutations, specifically MR genes, in sole +8 AML.

4 days ago

Clinical data • Journal

FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • STAG2 (Stromal Antigen 2)

ASXL1 mutation • TET2 mutation • SRSF2 mutation

Long read sequencing reveals novel isoforms and spliceosome-mutant-enriched transcripts in AML and MDS. (PubMed, bioRxiv)

This dataset is a valuable community resource, enabling detection of new transcripts in short read data sets. An interactive portal to explore splicing patterns in these data is available at https://leylab.org/isoforms/ .

6 days ago

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

CMML is in the eye of the be-WHO-lder: interrogating the newly proposed entity of oligomonocytic CMML: MDS or CMML? (PubMed, Blood Neoplasia)

Although O-CMML may be a unique entity, the current classification does not enrich CMML-like variants by all clinical measures. A comprehensive analysis of clinical, molecular and immunophenotype is needed for better classification.

7 days ago

Journal

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2)

TP53 mutation • SRSF2 mutation

21d

Molecular and clinical characteristics and prognosis of myelodysplastic neoplasms with biallelic TET2 inactivation (PubMed, Zhonghua Xue Ye Xue Za Zhi)

In contrast, no significant difference in OS was observed in the low-risk group (very low-risk, low-risk, and moderate low-risk) . Patients with MDS harboring biallelic TET2 inactivation exhibit distinct clinical and molecular characteristics and in patients with relatively high IPSS-M risk, their prognosis is worse than that of patients with monoallelic TET2 mutations.

21 days ago

Retrospective data • Journal

KRAS (KRAS proto-oncogene GTPase) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • CUX1 (cut like homeobox 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

ASXL1 mutation • TET2 mutation • SRSF2 mutation

23d

Genomic characterisation of Chinese myeloid malignancies and its clinical correlates: insights from targeted next-generation sequencing. (PubMed, Front Med (Lausanne))

These findings demonstrated associations between genetic alterations and clinical features, disease progression, and prognosis in Chinese patients with myeloid malignancies. However, the prognostic associations should be interpreted cautiously, as none of the evaluated variables remained independent prognostic factors in multivariate models.

23 days ago

Journal • Next-generation sequencing

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2C (Lysine Methyltransferase 2C) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • FAT1 (FAT atypical cadherin 1) • IL7R (Interleukin 7 Receptor) • SETBP1 (SET Binding Protein 1)

TP53 mutation • NPM1 mutation • ASXL1 mutation • SRSF2 mutation

29d

Determinants of survival in patients treated with CPX-351 for acute myeloid leukemia. (PubMed, Front Oncol)

Leukocytosis at diagnosis, complex karyotype, and mutations of IDH1 and SRSF2 were correlated with lower survival in the univariable analysis. In the multivariable analysis, leukocytosis and complex karyotype retained their statistical significance.

29 days ago

Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • SRSF2 (Serine and arginine rich splicing factor 2)

IDH1 mutation • SRSF2 mutation

Vyxeos (cytarabine/daunorubicin liposomal formulation)

Non-Enzymatic MGO-Glycation of SRSF2 Drives RNA Mis-Splicing. (PubMed, J Am Chem Soc)

Importantly, we found that these glycation events attenuate SRSF2's RNA binding and alter RNA splicing, phenocopying a recurrent leukemia oncogenic SRSF2 mutation, P95H. Collectively, our study resolves glycation as a bona fide, site-specific regulatory PTM for a splicing factor and provides the first evidence for MGO-mediated mis-splicing in living cells, suggesting a new mechanistic link between MGO-glycation and disease.

1 month ago

Journal

SRSF2 (Serine and arginine rich splicing factor 2)

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.

1 month 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.

1 month 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

1 month ago

Enrollment closed • Enrollment change

SF3B1 mutation • SRSF2 mutation

Reblozyl (luspatercept-aamt)

2ms

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.

2 months 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