Tyrosine kinase inhibitors (TKI) (midostaurin, avapritinib) have changed the treatment landscape in SM...Cladribine continues to have a role for MC debulking, whereas interferon-α has a diminishing role in the TKI era...Allogeneic stem cell transplant has a role in such patients. Imatinib has a therapeutic role only in the rare patient with an imatinib-sensitive KIT mutation.

18 hours ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • RUNX1 (RUNX Family Transcription Factor 1) • TNFRSF8 (TNF Receptor Superfamily Member 8) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • IL2RA (Interleukin 2 receptor, alpha) • CD2 (CD2 Molecule)

NRAS mutation • KIT mutation • ASXL1 mutation • TNFRSF8 expression • SRSF2 mutation

imatinib • midostaurin • cladribine • Ayvakit (avapritinib)

20h

Impact of U2AF1 Pathogenic Variants on Prognosis of Myelodysplastic Neoplasms With RUNX1 Mutation. (PubMed, Hematol Oncol)

Mutations in ASXL1, SRSF2, EZH2 and NRAS were significantly more frequent in RUNX1-mutated patients compared with those without RUNX1 mutations (adjusted p < 0.05). RUNX1-mutated patients exhibited poorer overall survival (median OS 18 months vs. 51 month, p < 0.001), while U2AF1 co-mutations were associated with a relatively better prognosis (median OS 34 months vs. 17 months, p = 0.003), indicating a potential modifying effect of U2AF1 on the outcome of RUNX1-mutated patients.

20 hours ago

Journal • Tumor mutational burden

TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

NRAS mutation • RUNX1 mutation • ASXL1 mutation • EZH2 mutation • SRSF2 mutation

Limited prognostic value of ELN classification and relevance of molecular ontogeny in acute myeloid leukemia post myeloproliferative neoplasms: a retrospective multicenter study. (PubMed, Acta Haematol)

ORR was 57%, 20% and 25% in patients treated by intensive chemotherapy (IC), hypomethylating agents (HMA) and BSC (including low intensity treatments as hydroxyurea and low-dose cytarabine), respectively. We observed poor outcome using IC or HMA encouraging us to propose new clinical trials in this specific subgroup. Only ASCT was able to improve prognosis.

4 days ago

Clinical • Retrospective data • Journal

JAK2 (Janus kinase 2) • SRSF2 (Serine and arginine rich splicing factor 2)

SRSF2 mutation

cytarabine • hydroxyurea

13d

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.

13 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

13d

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.

13 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

15d

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/ .

15 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

16d

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.

16 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

29d

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.

29 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

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.

1 month 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

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.

1 month 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