News - U2AF1 mutation

12d

SF3B1 Gene Mutations and Their Significance for Patients with Myelodysplastic Neoplasms (MDS) (ASH 2024)

Three are still alive and are undergoing azacitidine treatment at 6.5, 8.5, and 21 months after their diagnosis.Identification of splicing factor gene mutations is an important diagnostic tool for the stratification of MDS patients...Other biological factors such as the mutation variant, association with complex karyotypes, and mutations in other genes, may also affect the prognosis of patients with mutated SF3B1. Therefore, a comprehensive view that includes all cytogenomic, molecular, and clinical data is important for accurate diagnosis and personalized treatment of MDS patients.Supported by MH CZ-DRO 0064165

12 days ago

Clinical

TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • 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) • STAG2 (Stromal Antigen 2) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • BCORL1 (BCL6 Corepressor Like 1)

TP53 mutation • NRAS mutation • TET2 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • Chr del(5q) • SF3B1 K666N • SF3B1 K700E

Archer® VariantPlex® Myeloid panel

azacitidine

12d

Comprehensive Genomic Profiling (CGP) of Acute Myeloid Leukemias with Foundation One Heme Identifies Actionable Genomic Alterations and Biomarkers (ASH 2024)

Current best practices for the diagnosis, classification, prognostication, and treatment of AML call for the assessment of the presence and absence of numerous genomic alterations. Therefore, in contrast to single-gene or small-panel molecular testing, the F1H platform can simplify such assessment via a CGP approach.

12 days ago

IO biomarker

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • 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) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • BCOR (BCL6 Corepressor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • NUP214 (Nucleoporin 214) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • MRTFA (Myocardin Related Transcription Factor A) • RBM15 (RNA Binding Motif Protein 15)

TP53 mutation • NPM1 mutation • KMT2A rearrangement • MLL rearrangement • U2AF1 mutation • CEBPA mutation • MLL mutation • NPM1 W288

FoundationOne® Heme CDx

23d

Alternative Splicing: A Potential Therapeutic Target in Hematological Malignancies. (PubMed, Hematol Rep)

Mutations in splicing factors, such as U2AF1, SF3B1, SRSF2, ZRSR2, and HNRNPH1, are frequently observed across various hematological malignancies and are associated with poor prognosis and treatment resistance. This research underscores the necessity of understanding the mechanisms of RNA splicing dysregulation in order to develop targeted therapies to correct these aberrant processes, thereby improving outcomes for patients with leukemia and related disorders.

23 days ago

Review • 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) • HNRNPH1 (Heterogeneous Nuclear Ribonucleoprotein H1)

SF3B1 mutation • SRSF2 mutation • U2AF1 mutation

RNA splicing as a therapeutic target in myelodysplastic syndromes. (PubMed, Semin Hematol)

Emerging evidence shows that splicing factor-mutant cells are more sensitive to perturbations targeting the spliceosome, aberrantly spliced genes and/or their regulated molecular pathways. This review summarizes current therapeutic strategies and ongoing efforts targeting splicing factor mutations for the treatment of MDS.

1 month ago

Journal

SF3B1 mutation • SRSF2 mutation • U2AF1 mutation

DNA and RNA NGS for Myeloid Neoplasms Using Oncomine Myeloid Assay GX v2 on GeneXus: An Assessment of Clinical Utility (AMP 2024)

This DNA- and RNA-based 80-gene panel has proven to be a powerful tool for genomic profiling of myeloid neoplasms. The results were provided to hematopathologists/oncologists in timely fashion with the critical information for diagnosis confirmation, and disease classification, as well as assessment of patient response to treatment.

1 month ago

Clinical • Next-generation sequencing

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) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • 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) • DDX41 (DEAD-Box Helicase 41) • CALR (Calreticulin) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

FLT3-ITD mutation • NPM1 mutation • U2AF1 mutation • CEBPA mutation • JAK2 V617F

Oncomine Myeloid Assay GX

Development and Validation of a Biopsy-Free Scoring System for Screening Myelodysplastic Syndrome (MDS) and Associated Diseases in Cytopenic Patients (ASH 2024)

For patients with a probability score < 45%, a bone marrow study may not be needed, with a recommended follow-up every 6–12 months. This comprehensive analysis provides a useful and non-invasive predictive model that enhances diagnostic accuracy which potentially reduces unnecessary procedures.

1 month ago

Clinical • Biopsy

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) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • 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) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • KRAS mutation • NRAS mutation • IDH2 mutation • NPM1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation

Oncomine Myeloid Research Assay

2ms

Prognostic impact of next-generation sequencing on myelodysplastic syndrome: A single-center experience. (PubMed, Medicine (Baltimore))

According to early findings, NGS panels are extremely effective instruments that provide an entirely new viewpoint on the disease for particular individuals. Future prognostications will depend more on NGS because those who exhibit normal cytogenetics may additionally have gene mutations.

2 months ago

Journal • Next-generation sequencing

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • 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) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • PHF6 (PHD Finger Protein 6)

ASXL1 mutation • TET2 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • PHF6 mutation

2ms

Commitment Complex Splicing Factors in Cancers of the Gastrointestinal Tract-An In Silico Study. (PubMed, Bioinform Biol Insights)

This study demonstrates the versatility of in silico analysis to determine molecular function of large macromolecular complexes such as the spliceosome CC. Furthermore, our analysis indicates that therapeutic lowering of CC levels in colon cancer patients may enhance patient survival.

2 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

TP53 mutation • KRAS mutation • BRAF mutation • U2AF1 mutation

Intron A (interferon α-2b)

2ms

Hyperactivation of NF-κB signaling in splicing factor mutant myelodysplastic syndromes and therapeutic approaches. (PubMed, Adv Biol Regul)

The potent IRAK4 inhibitor CA-4948 has shown efficacy in both pre-clinical studies and MDS clinical trials, with splicing factor mutant patients showing the higher response rates. Emerging data has, however, revealed that co-targeting of IRAK4 and its paralog IRAK1 is required to maximally suppress LSPC function in vitro and in vivo by inducing cellular differentiation. These findings provide a link between the presence of the commonly mutated splicing factor genes and activation of innate immune signaling pathways in myeloid malignancies and have important implications for targeted therapy in these disorders.

2 months ago

Journal

SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • IRAK4 (Interleukin 1 Receptor Associated Kinase 4)

SF3B1 mutation • SRSF2 mutation • U2AF1 mutation

emavusertib (CA-4948)

2ms

Therapeutic strategies targeting aberrant RNA splicing in myeloid malignancies. (PubMed, Br J Haematol)

Mutations in spliceosomal components have been identified in numerous cancer subtypes, with mutations in RNA binding proteins SF3B1, SRSF2, U2AF1, and ZRSR2 occurring frequently in AML and in up to 60% of patients with MDS, as well as in chronic myelomonocytic leukaemia and in 10% of patients with chronic lymphocytic leukaemia. In this review, we explore therapeutic strategies targeting aberrant splicing and the potential of these approaches to drive clinical responses.

2 months ago

Review • Journal

SF3B1 mutation • SRSF2 mutation • U2AF1 mutation

3ms

PHF6 mutations in chronic myelomonocytic leukemia identify a unique subset of patients with distinct phenotype and superior prognosis. (PubMed, Am J Hematol)

The specific molecular signatures sustained their significant predictive performance in the context of the CMML-specific molecular prognostic model (CPSS-mol). PHF6MUT identifies a unique subset of patients with CMML characterized by thrombocytopenia, higher prevalence of LoY, and superior prognosis.

3 months ago

Journal

DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • PHF6 (PHD Finger Protein 6)

SRSF2 mutation • U2AF1 mutation • PHF6 mutation

3ms

U2AF1 S34F enhances tumorigenic potential of lung cells by exhibiting synergy with KRAS mutation and altering response to environmental stress. (PubMed, bioRxiv)

Interestingly, HBEC3kts harboring only U2AF1 S34F display increased splicing in stress granule protein genes and viability in cigarette smoke concentrate. Our results suggest that U2AF1 S34F may potentiate transformation by granting precancerous cells survival advantage in environmental stress, permitting accumulation of additional mutations like KRAS G12V , which synergize with U2AF1 S34F to transform the cell.

3 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

KRAS mutation • KRAS G12V • KRAS G12 • U2AF1 mutation • U2AF1 S34F

3ms

Distinct mutation features and its clinical significance in myelodysplastic syndromes with normal karyotype. (PubMed, Ann Hematol)

In summary, MDS with NK showed distinct mutation features from those with AK. High-frequency gene mutations together with the mutational evolution suggested the diagnostic and monitoring significance of next generation sequencing for NK-MDS.

3 months ago

Journal

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

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

3ms

Phase I/II study of the clinical activity and safety of GSK3326595 in patients with myeloid neoplasms. (PubMed, Ther Adv Hematol)

The safety profile was broadly consistent with other published PRMT5 inhibitor studies. ClinicalTrials.gov: NCT03614728.

3 months ago

P1/2 data • Journal

SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

SRSF2 mutation • U2AF1 mutation

pemrametostat (GSK3326595)

3ms

Prognostic impact of DTA mutation and co-occurring mutations in patients with myelodysplastic syndrome. (PubMed, Mol Biol Rep)

DTA mutations are frequently observed in patients with MDS, often accompanied by genes involved in RNA splicing and transcription factors like SF3B1 and RUNX1. DTA and concomitant mutations affect prognosis in MDS patients and RUNX1 was identified as an independent poor prognostic factor in patients with DTA mutations.

3 months ago

Retrospective data • Journal

TP53 (Tumor protein P53) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • 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) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1)

TP53 mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 mutation • U2AF1 mutation

3ms

Long-term longitudinal analysis of 4,187 participants reveals insights into determinants of clonal hematopoiesis. (PubMed, Nat Commun)

This study also reveals associations between germline genetic variants and incident CHIP. Our comprehensive longitudinal assessment yields insights into cell-intrinsic and -extrinsic factors contributing to the development and progression of CHIP clones in older adults.

3 months ago

Journal

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) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

U2AF1 mutation • DNMT3A R882

7ms

Biological relevance of alternative splicing in hematologic malignancies. (PubMed, Mol Med)

In this review, we discuss aberrant splicing events induced by mutations affecting SFs (SF3B1, U2AF1, SRSR2, and ZRSR2), spliceosome components (PRPF8, LUC7L2, DDX41, and HNRNPH1), and epigenetic modulators (IDH1 and IDH2). Finally, we provide an extensive overview of the biological relevance of aberrant isoforms of genes involved in the regulation of apoptosis (e. g. BCL-X, MCL-1, FAS, and c-FLIP), activation of key cellular signaling pathways (CASP8, MAP3K7, and NOTCH2), and cell metabolism (PKM).

7 months ago

Review • Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • SF3B1 (Splicing Factor 3b Subunit 1) • BCL2L1 (BCL2-like 1) • NOTCH2 (Notch 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • DDX41 (DEAD-Box Helicase 41) • CASP8 (Caspase 8) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • HNRNPH1 (Heterogeneous Nuclear Ribonucleoprotein H1) • MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7) • PRPF8 (Pre-MRNA Processing Factor 8)

SF3B1 mutation • U2AF1 mutation

7ms

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.

7 months 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

7ms

Efficacy and safety of venetoclax combined with hypomethylating agents in the treatment of 83 patients with higher-risk myelodysplastic syndromes (PubMed, Zhonghua Xue Ye Xue Za Zhi)

VEN combined with HMA had a high response rate in patients with HR-MDS, both at initial treatment and with HMA failure. ALP ≥ 90 U/L, TP53 mutation, and U2AF1 mutation were independent risk factors for non-response to treatment.

7 months ago

Retrospective data • Journal

TP53 (Tumor protein P53) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

TP53 mutation • U2AF1 mutation

Venclexta (venetoclax)

8ms

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.

8 months 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

8ms

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.

8 months 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)

8ms

Erythroid predominance in bone marrow biopsies of AML patients after decitabine treatment correlates with mutation profile and complete remission. (PubMed, Pathobiology)

We conclude that early histological bone marrow examination for the development of an EDR may be helpful to predict response in AML patients during treatment with DAC.

8 months ago

Journal • Biopsy

RUNX1 (RUNX Family Transcription Factor 1) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

RUNX1 mutation • U2AF1 mutation

decitabine

8ms

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.

8 months 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

8ms

What is new in acute myeloid leukemia classification? (PubMed, Blood Res)

AML cases defined by differentiation (WHO2022) and AML not otherwise specified (ICC) are categorized as lacking specific defining genetic abnormalities, WHO2022 labels this as a myeloid neoplasm post cytotoxic therapy (MN-pCT), described as an appendix after specific diagnosis. Similarly, in ICC, it can be described as "therapy-related", without a separate AML category.

8 months ago

Review • Journal

TP53 (Tumor protein P53) • ABL1 (ABL proto-oncogene 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) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • U2AF1 mutation • CEBPA mutation

8ms

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.

8 months 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)

8ms

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

8 months 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)

9ms

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

9 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

9ms

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.

9 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

9ms

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.

9 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

9ms

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

9 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

9ms

AZD6738 for Patients With Progressive MDS or CMML (clinicaltrials.gov)

P1, N=52, Recruiting, Massachusetts General Hospital | Trial primary completion date: May 2022 --> May 2024

9 months ago

Trial primary completion date

SF3B1 mutation • U2AF1 mutation

ceralasertib (AZD6738)

10ms

Profiling the splicing landscape in solid tumors in a large, real-world dataset (AACR 2024)

This work revealed the presence of multiple SPs - characterized by distinct clinical and molecular traits. Further work will be able to contextualize STT response data using SPs to facilitate STT biomarker discovery.

10 months ago

Real-world evidence • Clinical • Real-world

MYC (V-myc avian myelocytomatosis 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)

MYC expression • U2AF1 mutation

Tempus xR

10ms

Molecular and clinical analyses of PHF6 mutant myeloid neoplasia provide their pathogenesis and therapeutic targeting. (PubMed, Nat Commun)

Finally, we demonstrate a negative prognostic role of PHF6MT, especially in association with RUNX1. The negative effects on survival are additive as PHF6MT cases with RUNX1 mutations have worse outcomes when compared to cases carrying single mutation or wild-type.

10 months ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • PHF6 (PHD Finger Protein 6)

RUNX1 mutation • ASXL1 mutation • U2AF1 mutation • PHF6 mutation

10ms

Mutant U2AF1-induced mis-splicing of mRNA translation genes confers resistance to chemotherapy in acute myeloid leukemia. (PubMed, Cancer Res)

A pharmacologic inhibitor of ISR, ISRIB, sensitized U2AF1 mutant cells to chemotherapy. These findings highlight a resistance mechanism by which U2AF1 mutations drive chemoresistance and provide a therapeutic approach for AML through targeting the ISR pathway.

10 months ago

Journal

U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

U2AF1 mutation • U2AF1 S34F

10ms

The Correlation of Gene Mutation and Clinical Characteristics in Patients with Myelodysplastic Syndrome and Prognostic Analysis (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

Gene mutation is closely related to cytogenetic indexes and clinical features (peripheral blood cell count, sex, age). IPSS-R prognostic score and TP53 were risk factors affecting OS in MDS patients.

10 months ago

Journal

TP53 (Tumor protein P53) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 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) • WT1 (WT1 Transcription Factor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • SETBP1 (SET Binding Protein 1)

TP53 mutation • TP53 wild-type • ASXL1 mutation • SF3B1 mutation • U2AF1 mutation

10ms

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.

10 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

10ms

CEBPA double mutations associated with ABO antigen weakness in hematologic diseases. (PubMed, Blood Adv)

Among these, CEBPA double mutations displayed a significant association, with ABO antigen weakness being observed in 20 out of the 25 individuals (80.0%) possessing these mutations. From this study, new factors associated with ABO antigen weakness have been identified.

10 months ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

U2AF1 mutation • CEBPA mutation

11ms

Primary myelofibrosis with double mutation in U2AF1 (PubMed, Rinsho Ketsueki)

Although U2AF1 gene abnormality is known as a poor prognostic factor in primary myelofibrosis, this patient had a favorable long-term prognosis due to prompt transplantation therapy. This case highlights the importance of detailed gene mutation analysis in patients with triple-negative MF.

11 months ago

Journal

JAK2 (Janus kinase 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CALR (Calreticulin)

U2AF1 mutation • U2AF1 S34F

11ms

Genetic landscape and clinical outcomes of patients with BCOR mutated myeloid neoplasms. (PubMed, Haematologica)

However, RUNX1 co-mutation was associated with an increased risk of post-alloSCT relapse (HR 88.0, P = 0.02), whereas melphalan-based conditioning was associated with a decreased relapse-risk (HR 0.02, P = 0.01). We conclude that mBCOR is a high-risk feature across MDS/AML and that alloSCT improves survival in this population.

11 months ago

Clinical data • Journal

TP53 (Tumor protein P53) • RUNX1 (RUNX Family Transcription Factor 1) • BCL6 (B-cell CLL/lymphoma 6) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

TP53 mutation • RUNX1 mutation • U2AF1 mutation • BCOR mutation

melphalan

11ms

Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN (clinicaltrials.gov)

P1, N=100, Recruiting, Jacqueline Garcia, MD | Trial completion date: Dec 2024 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Feb 2025

11 months ago

Trial completion date • Trial primary completion date • Combination therapy

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCR (BCR Activator Of RhoGEF And GTPase) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • 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) • DEK (DEK Proto-Oncogene) • RIT1 (Ras Like Without CAAX 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • KRAS mutation • NRAS mutation • RUNX1 mutation • RAS mutation • ASXL1 mutation • CBL mutation • MLL rearrangement • U2AF1 mutation • Chr del(5q) • FLT3 wild-type

Venclexta (venetoclax) • azacitidine • Inqovi (decitabine/cedazuridine) • fludarabine IV • busulfan

11ms

Analysis of gene mutation characteristics and its correlation with prognosis in patients with myelodysplastic syndromes. (PubMed, Clin Chim Acta)

Additionally, the study developed a risk score based on gene mutation data that demonstrated robust predictive capability and stability for the overall survival of MDS patients. Our research provided a strong theoretical basis for the establishment of personalized treatment and prognostic risk assessment models for Chinese MDS patients.

11 months ago

Journal

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)

TP53 mutation • DNMT3A mutation • ASXL1 mutation • SF3B1 mutation • U2AF1 mutation • ETV6 mutation

12ms

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.

12 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