News - SRSF2 mutation

CLONAL EVOLUTION IN SECUNDARY ACUTE MYELOID LEUKEMIA ARISING FROM MYELOPROLIFERATIVE NEOPLASMS (EHA 2024)

Our data suggest that secondary AML arising from MPNs is a genetically distinct entity compared to de novoAML, with a higher incidence of mutations in high-risk genes such as TP53, a high rate of relapse/refractorinessand poor prognosis with current therapeutic strategies. NGS determination of somatic mutations could identifyhigh-risk-progression patients, and monitoring these mutations could be useful, along with other clinical data,to anticipate progression.

6 days ago

TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CALR (Calreticulin)

TP53 mutation • RUNX1 mutation • SRSF2 mutation • U2AF1 mutation • JAK2 V617F • CALR mutation

Oncomine Myeloid Research Assay

STUDY OF THE MOLECULAR GENETIC PROFILE OF HIGH-RISK AML PATIENTS USING NEXT GENERATION SEQUENCING (EHA 2024)

Highly heterogeneous molecular genetic profile is present in patients from adverse risk group. Mutations ingenes that activate intracellular signaling pathways are most common in high-risk AML. The presence of morethan 6 mutations and ASXL1mut+ and SRSF2mut+ status negatively affect the survival of patients.

6 days ago

Clinical • Next-generation sequencing

TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • NF1 (Neurofibromin 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) • KMT2C (Lysine Methyltransferase 2C) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • FAT1 (FAT atypical cadherin 1) • CUX1 (cut like homeobox 1)

TP53 mutation • DNMT3A mutation • ASXL1 mutation • PTPN11 mutation • SRSF2 mutation

TruSight Myeloid Sequencing Panel

13d

Predicting survival in patients with myelodysplastic/myeloproliferative neoplasms with SF3B1 mutation and thrombocytosis. (PubMed, Leukemia)

According to the univariable analyses of OS, age ≥ 65 years (P < 0.001), hemoglobin concentration (Hb) < 80 g/L (P = 0.090), platelet count (PLT) ≥ 800 × 10E + 9/L (P = 0.087), bone marrow RS < 15% (P < 0.001), the Revised International Prognostic Scoring System (IPSS-R) cytogenetic category intermediate/poor/very poor (P = 0.005), SETBP1 mutation (P = 0.061) and SRSF2 mutation (P < 0.001) were associated with poor survival. Based on variables selected from univariable analyses, two separate survival prediction models, a clinical survival model, and a clinical-molecular survival model, were developed using multivariable analyses with the minimum value of the Akaike information criterion (AIC) to specifically predict outcomes in patients with MDS/MPN-SF3B1-T according to the 2022 WHO classification.

13 days ago

Journal

SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2) • SETBP1 (SET Binding Protein 1)

SF3B1 mutation • SRSF2 mutation • SETBP1 mutation

13d

A mitochondrial surveillance mechanism activated by SRSF2 mutations in hematologic malignancies. (PubMed, J Clin Invest)

Inhibition of splicing with a glycogen synthase kinase 3 inhibitor promoted retention of the poison intron, impairing mitophagy and activating apoptosis in SRSF2P95H/+ cells. These data reveal a homeostatic mechanism for sensing mitochondrial stress through PINK1 splicing and identify increased mitophagy as a disease marker and a therapeutic vulnerability in SRSF2P95H mutant MDS and AML.

13 days ago

Journal

SRSF2 (Serine and arginine rich splicing factor 2) • PINK1 (PTEN Induced Kinase 1)

SRSF2 mutation • SRSF2 P95H

25d

A comparative analysis of the clinical and genetic profiles of blast phase BCR::ABL1-negative myeloproliferative neoplasm and acute myeloid leukemia, myelodysplasia-related. (PubMed, Int J Lab Hematol)

MPN-BP and AML-MR harbor similar somatic mutations and clinical outcomes, suggesting a unified clinical disease entity.

25 days ago

Journal

TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 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) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • SETBP1 (SET Binding Protein 1) • CALR (Calreticulin)

TP53 mutation • DNMT3A mutation • ASXL1 mutation • TET2 mutation • SRSF2 mutation • U2AF1 mutation

26d

A novel t(X;21)(p11.4;q22.12) translocation adds to the role of BCOR and RUNX1 in myelodysplastic syndromes and acute myeloid leukemias. (PubMed, Genes Chromosomes Cancer)

Whole transcriptome analysis showed that overexpression of HOXA9 differentiated t(X;21) from both controls and t(8;21)-positive AML. In conclusion, we characterized a new recurrent reciprocal t(X;21)(p11.4;q22.12) chromosome translocation in MDS and AML, generating simultaneous BCOR and RUNX1 deletions rather than a fusion gene at the genomic level.

26 days ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • HOXA9 (Homeobox A9) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TET2 mutation • EZH2 mutation • SRSF2 mutation

28d

Caspase 8 deletion causes infection/inflammation-induced bone marrow failure and MDS-like disease in mice. (PubMed, Cell Death Dis)

Most importantly, mice transplanted with Casp8-/- BM cells developed MDS-like disease within 4 months of transplantation as demonstrated by anemia, thrombocytopenia and myelodysplasia. Our study suggests an essential role for a balance in Casp8, Ripk3-Mlkl and Ripk1-Tbk1 activities in the regulation of survival and self-renewal of HSPCs, the disruption of which induces inflammation and BM failure, resulting in MDS-like disease.

28 days ago

Preclinical • Journal

SRSF2 (Serine and arginine rich splicing factor 2) • CASP8 (Caspase 8) • RIPK1 (Receptor Interacting Serine/Threonine Kinase 1)

SRSF2 mutation

28d

Chronic neutrophilic leukemia and atypical chronic myeloid leukemia: 2024 update on diagnosis, genetics, risk stratification, and management. (PubMed, Am J Hematol)

Most commonly used agents include hydroxyurea, interferon, Janus kinase inhibitors, and hypomethylating agents, though none are disease-modifying. Actionable mutations (NRAS/KRAS, ETNK1) have also been identified, supporting novel agents targeting involved pathways. Preclinical and clinical studies evaluating new drugs (e.g., fedratinib, phase 2) and combinations are detailed.

28 days ago

Review • Journal

KRAS (KRAS proto-oncogene GTPase) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CSF3R (Colony Stimulating Factor 3 Receptor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • SETBP1 (SET Binding Protein 1) • ETNK1 (Ethanolamine Kinase 1)

KRAS mutation • NRAS mutation • ASXL1 mutation • TET2 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • CSF3R T618I • CSF3R mutation • ETNK1 mutation

hydroxyurea • Inrebic (fedratinib)

Analysis of CSF3R mutations in atypical chronic myeloid leukemia and other myeloid malignancies. (PubMed, Ann Diagn Pathol)

In conclusion, CSF3R mutations were found at a higher frequency in aCML patients than in previous studies, which might reflect ethnic differences. Additional studies are needed to confirm these findings and the relationship between CSF3R and CEBPA mutations.

1 month ago

Journal

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)

ASXL1 mutation • SRSF2 mutation • CEBPA mutation • CSF3R T618I • CSF3R mutation

Poor prognosis of SRSF2 gene mutations in patients treated with VEN-AZA for newly diagnosed acute myeloid leukemia. (PubMed, Leuk Res)

This study aimed to evaluate the impact of Spliceosome mutations in patients treated with Venetoclax and Azacitidine for newly diagnosed AML. This negative prognostic impact remained true in our multivariate analysis. We believe this finding should warrant further studies aimed at overcoming this negative impact.

1 month ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog) • 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)

NRAS mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation

Venclexta (venetoclax) • azacitidine

Accelerated DNA replication fork speed due to loss of R-loops in myelodysplastic syndromes with SF3B1 mutation. (PubMed, Nat Commun)

Importantly, histone deacetylase inhibition using vorinostat restores R-loop formation, slows down DNA replication forks and improves SF3B1-mutated erythroblast differentiation. In conclusion, loss of R-loops with associated DNA replication stress represents a hallmark of SF3B1-mutated MDS ineffective erythropoiesis, which could be used as a therapeutic target.

1 month 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 • U2AF1 mutation

Zolinza (vorinostat)

RBM10 C761Y mutation induced oncogenic ASPM isoforms and regulated β-catenin signaling in cholangiocarcinoma. (PubMed, J Exp Clin Cancer Res)

Our results showed that RBM10C761Y-modulated ASPM203 promoted CCA progression in a Wnt/β-catenin signaling-dependent manner. This study may enhance the understanding of the regulatory mechanisms that link mutation-altering splicing variants to CCA.

1 month ago

Journal

SRSF2 (Serine and arginine rich splicing factor 2) • RBM10 (RNA Binding Motif Protein 10)

SRSF2 mutation • RBM10 mutation

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: Aug 2024 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Aug 2025

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 • MLL rearrangement • SRSF2 mutation • U2AF1 mutation • BCOR mutation • Chr del(5q) • STAG2 mutation • FLT3 wild-type • Chr t(9;11) • ZRSR2 mutation

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

2ms

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 | N=55 --> 80

2 months ago

Enrollment change

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 • DNMT3A mutation • TET2 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation

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

2ms

Targeting SRSF2 mutations in leukemia with RKI-1447: A strategy to impair cellular division and nuclear structure. (PubMed, iScience)

The severe nuclear deformation in RKI-1447-treated SRSF2 mutant cells prevents cells from completing mitosis. These findings shed new light on the interplay between microtubules and the nucleus and offers new ways for targeting pre-leukemic SRSF2 mutant cells.

2 months ago

Journal

SRSF2 (Serine and arginine rich splicing factor 2)

SRSF2 mutation

2ms

Differential prognostic values of the three AKT isoforms in acute myeloid leukemia. (PubMed, Sci Rep)

Curiously, although modestly varying among AML samples, a high AKT1 expression shows in contrast as a strong predictor of a better patient outcome. These data suggest that AKT3 and AKT1 expressions have strong, yet opposite, prognostic values.

2 months ago

Journal

NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • AKT3 (V-akt murine thymoma viral oncogene homolog 3)

NPM1 mutation • RUNX1 mutation • ASXL1 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • BCOR mutation • AKT2 expression • AKT3 expression

2ms

Triple-Negative Myelofibrosis: Disease Features, Response to Treatment and Outcomes. (PubMed, Clin Lymphoma Myeloma Leuk)

TN-MF is invariably associated with significantly decreased survival and more aggressive clinical behavior with higher rates of leukemic transformation and shorter duration of response to ruxolitinib. Mutations impacting RNA splicing, epigenetic modification and signaling (SRSF2, SETBP1, IDH2, CBL, and GNAS) are more common in TN-MF, which likely drive its aggressive course and may account for suboptimal responses to JAK inhibition.

2 months ago

Journal

ABL1 (ABL proto-oncogene 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • SETBP1 (SET Binding Protein 1) • GNAS (GNAS Complex Locus) • CALR (Calreticulin)

ASXL1 mutation • SRSF2 mutation • LDH-L

Jakafi (ruxolitinib)

2ms

A Study of Alternative TrkA Splicing Identifies TrkAIII as a Novel Potentially Targetable Participant in PitNET Progression. (PubMed, Biology (Basel))

Therefore, TrkAIII splicing is common in PitNETs, is elevated in invasive, especially PIT1 tumors, can result in intracellular TrkAIII activation, and may involve hypoxia. The data support a role for TrkAIII splicing in PitNET pathogenesis and progression and identify TrkAIII as a novel potential target in refractory PitNETs.

2 months ago

Journal

SF3B1 (Splicing Factor 3b Subunit 1) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • EPAS1 (Endothelial PAS domain protein 1) • XBP1 (X-box-binding protein 1)

SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • HIF1A expression • NTRK expression

2ms

Ascorbic Acid and Combination Chemotherapy for the Treatment of Relapsed or Refractory Lymphoma or CCUS (clinicaltrials.gov)

P2, N=55, Recruiting, Mayo Clinic | Trial completion date: Mar 2024 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Dec 2025

2 months ago

Trial completion date • Trial primary completion date

IDH2 mutation • DNMT3A mutation • TET2 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation

cisplatin • carboplatin • gemcitabine • Rituxan (rituximab) • cytarabine • cyclophosphamide • ifosfamide • oxaliplatin • etoposide IV • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate) • dexamethasone injection

2ms

Chronic myelomonocytic leukemia: 2024 update on diagnosis, risk stratification and management. (PubMed, Am J Hematol)

Drug therapy is currently not disease-modifying and includes hydroxyurea and hypomethylating agents; a recent phase-3 study (DACOTA) comparing hydroxyurea and decitabine, in high-risk MP-CMML, showed similar overall survival at 23.1 versus 18.4 months, respectively, despite response rates being higher for decitabine (56% vs. 31%). These include systemic inflammatory autoimmune diseases, leukemia cutis and lysozyme-induced nephropathy; the latter requires close monitoring of renal function during leukocytosis and is a potential indication for cytoreductive therapy.

2 months ago

Journal

DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2)

DNMT3A mutation • ASXL1 mutation • TET2 mutation • SRSF2 mutation

decitabine • hydroxyurea

3ms

A comprehensive genomic profiling of myeloid malignancies demonstrates mutational spectrum of DNA variants, FLT3-ITDs, and gene fusions (AACR 2024)

The Oncomine Myeloid Assay is a fast, robust, and reproducible solution for comprehensive genomic profiling of myeloid malignancies. We describe the mutational spectrum of DNA variants and RNA fusions in a range of clinical research samples. (For research use only.

3 months ago

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR1 (Fibroblast growth factor receptor 1) • DNMT3A (DNA methyltransferase 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CREBBP (CREB binding protein) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • ZMYM2 (Zinc Finger MYM-Type Containing 2) • CALR (Calreticulin) • KAT6A (Lysine Acetyltransferase 6A) • ANKRD26 (Ankyrin Repeat Domain Containing 26)

FLT3-ITD mutation • ASXL1 mutation • TET2 mutation • SRSF2 mutation • FGFR1 fusion

Oncomine Myeloid Assay GX • Oncomine Myeloid Research Assay

3ms

Broad next generation integrated sequencing of myelofibrosis identifies disease-specific and age-related genomic alterations. (PubMed, Clin Cancer Res)

Our results illustrate that evolution of MF from ET/PV/PrePMF likely advances with age, accumulation of mutations, and activation of proliferative pathways. The genes and pathways identified by integrated genomics approach provide insight into disease transformation and progression, and potential targets for therapeutic intervention.

3 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCR (BCR Activator Of RhoGEF And GTPase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NF1 (Neurofibromin 1) • 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) • ELTD1 (Adhesion G Protein-Coupled Receptor L4) • DNASE1L3 (Deoxyribonuclease 1 Like 3)

KRAS mutation • NRAS mutation • NF1 mutation • RAS mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation

5ms

Discovery of U2AF1 neoantigens in myeloid neoplasms. (PubMed, J Immunother Cancer)

These data serve as proof-of-concept for developing precision medicine approaches that use neoantigen-directed T-cell receptor-transduced T cells to treat MDS and sAML.

5 months ago

Journal • IO biomarker

CD8 (cluster of differentiation 8) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

SRSF2 mutation • U2AF1 mutation

5ms

Predicting cytopenias, progression, and survival in patients with clonal cytopenia of undetermined significance: a prospective cohort study. (PubMed, Lancet Haematol)

Mutation analysis is advised in patients who have undergone bone marrow examination and have an otherwise-unexplained cytopenia. High-risk genetic mutations and increased numbers of mutations are predictive of both survival and progression within 5 years of presentation, warranting clinical surveillance and, when necessary, intervention.

5 months ago

Journal

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • DDX41 (DEAD-Box Helicase 41)

TP53 mutation • DNMT3A mutation • ASXL1 mutation • SRSF2 mutation

5ms

Prognosis and risk factors for ASXL1 mutations in patients with newly diagnosed acute myeloid leukemia and myelodysplastic syndrome. (PubMed, Cancer Med)

Our study indicated that mutations in G646W or RUNX1 co-mutations are closely associated with a dismal clinical outcome in patients with AML and MDS harboring ASXL1 . Considering the poor prognosis and risk factors in patients with ASXL1 , more available treatments should be pursued.

5 months ago

Journal

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) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1)

NRAS mutation • RUNX1 mutation • ASXL1 mutation • EZH2 mutation • SRSF2 mutation • STAG2 mutation

5ms

Metformin: A potential adjunct for treatment of systemic mastocytosis. (PubMed, J Allergy Clin Immunol Glob)

In vitro results showed that metformin inhibited the proliferation of both cell lines; HMC-1.1 cells were more sensitive to metformin. These preliminary findings suggest that early use of metformin to target CSCs has the possibility to complement current treatments available for SM.

5 months ago

Journal

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

SRSF2 mutation

metformin

5ms

Clinical and pathological features of clonal cytopenia of undetermined significance presenting with isolated thrombocytopenia (CCUS-IT). (PubMed, Eur J Haematol)

We describe the clinicopathological features of CCUS-IT which can mimic immune thrombocytopenia.

5 months ago

Journal

SRSF2 (Serine and arginine rich splicing factor 2)

SRSF2 mutation

5ms

SRSF2 plays an unexpected role as reader of mC on mRNA, linking epitranscriptomics to cancer. (PubMed, Mol Cell)

In leukemia patients, low NSUN2 expression leads to mRNA mC hypomethylation and, combined with SRSF2, predicts poor outcomes. Altogether, we highlight an unrecognized mechanistic link between epitranscriptomics and a key oncogenesis driver.

5 months ago

Journal

SRSF2 (Serine and arginine rich splicing factor 2) • NSUN2 (NOP2/Sun RNA Methyltransferase 2)

SRSF2 mutation

6ms

Clonal hematopoiesis and its evolution of myeloproliferative neoplasms (PubMed, Zhonghua Yi Xue Za Zhi)

Although great progress has been made in the understanding of MPN clonal hematopoiesis and its evolution with the development of next-generation sequencing, there are still many limitations. In this study, we mainly discuss gene mutations of MPN and their influences on the thrombosis, leukemia and fibrosis transformation, and the influencing factors of clonal evolution, aiming to summarize the influence of clonal hematopoiesis and its evolution on the complications, prognosis and survival of MPN.

6 months ago

Journal

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CALR (Calreticulin)

TP53 mutation • DNMT3A mutation • ASXL1 mutation • SF3B1 mutation • SRSF2 mutation • JAK2 mutation • CALR mutation

6ms

Correlation of TCR Repertoire Diversity with Myeloid Gene Mutations in Chronic and Advanced Phase Myeloproliferative Neoplasms (ASH 2023)

APs of MPNs show an abnormal TCR diversity pattern. This pattern may be related to the acquisition of myeloid gene mutations in AP. To our knowledge, this is the first study demonstrating an alteration in TCR diversity in AP and opens the door to future fields of research.

6 months ago

IO biomarker • Metastases

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • CALR (Calreticulin)

SRSF2 mutation

6ms

Bone Marrow Cytokines Concentrations in Myelodysplastic Neoplasms: Its Correlation with the Immune Populations and Clonal Hematopoiesis (ASH 2023)

Our study describes a heterogenic Background of MDS. Suggesting an increase in some cytokines related to cell recruitment, migration, and proliferation in the bone marrow of MDS and an exhaustive and inhibitory environment in those patients with high-risk characteristics, pointing out the important role of immune subpopulations and environment in the clonal progression.

6 months ago

Clinical • IO biomarker

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CD8 (cluster of differentiation 8) • TET2 (Tet Methylcytosine Dioxygenase 2) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • SRSF2 (Serine and arginine rich splicing factor 2) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • IL2RA (Interleukin 2 receptor, alpha) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • IL2 (Interleukin 2) • IL7R (Interleukin 7 Receptor) • NCAM1 (Neural cell adhesion molecule 1) • IL10 (Interleukin 10) • CCR7 (Chemokine (C-C motif) receptor 7) • CD27 (CD27 Molecule) • FGF2 (Fibroblast Growth Factor 2) • CCL11 (C-C Motif Chemokine Ligand 11) • CCL2 (Chemokine (C-C motif) ligand 2) • CSF2 (Colony stimulating factor 2) • PHF6 (PHD Finger Protein 6) • IL17A (Interleukin 17A) • IL1A (Interleukin 1, alpha) • CXCR3 (C-X-C Motif Chemokine Receptor 3) • CXCR6 (C-X-C Motif Chemokine Receptor 6) • IL13 (Interleukin 13) • IL15 (Interleukin 15) • IL1B (Interleukin 1, beta) • IL1R1 (Interleukin 1 receptor, type I) • IL22 (Interleukin 22) • IL4 (Interleukin 4) • IL5 (Interleukin 5) • IL7 (Interleukin 7) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

SRSF2 mutation

Oncomine Myeloid Research Assay

6ms

Characterization of Cases with the Rare Cytogenetic Abnormality I(7)(p10) Reveals an Association with IDH2 Mutated Acute Myeloid Leukemia (ASH 2023)

(1) The rare but recurrent cytogenetic aberration i(7)(p10) is mainly found in AML, where associations with mutations in IDH2, DNMT3A and BCOR were observed. By contrast, other AML-defining mutations ( NPM1, FLT3-ITD, CEPBA) were largely absent, further no defining fusions/rearrangements or a complex karyotype were detected. (2) The vast majority of patients were female and younger than patients with IDH2 mutation without i(7)(p10).

6 months ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • ARG1 (Arginase 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

FLT3-ITD mutation • IDH1 mutation • IDH2 mutation • NPM1 mutation • DNMT3A mutation • ASXL1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • STAG2 mutation • DNMT3A mutation + IDH mutation

6ms

Comprehensive Molecular Stratification of Patients with AML Treated with CPX-351 (ASH 2023)

Among patients with AML treated with CPX-351, PTPN11 and IDH2 mutations were independently associated with inferior overall survival compared to those without these mutations. The PTPN11 gene is involved in RAS pathway regulation and has also been associated with shorter survival in AML in other studies. Here, mutated SRSF2 was associated with improved survival after CPX-351 induction.

6 months ago

Clinical

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2)

TP53 mutation • FLT3-ITD mutation • IDH2 mutation • ASXL1 mutation • TET2 mutation • PTPN11 mutation • SRSF2 mutation

Vyxeos (cytarabine/daunorubicin liposomal formulation)

6ms

Mutational Burden in High Risk Genes Do Not Affect Remission Rates and MRD Clearance in Elderly AML Patients Receiving CPX-351 Induction (ASH 2023)

CPX-351 is able to induce good quality remission with high CR rate and MRD negativity, regardless of mutational burden, allowing a high number of elderly AML patients to undergo to HSCT. MRD evaluation has proven to be a strong prognostic tool also in the setting of elderly s-AML and t-AML patients receiving CPX-351. The prognostic value of high risk mutation seems to be less relevant in CPX-351 treated patients.

6 months ago

Clinical • Tumor mutational burden

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2)

TP53 mutation • TMB-H • RUNX1 mutation • SRSF2 mutation

Vyxeos (cytarabine/daunorubicin liposomal formulation)