^
Contact us  to learn more about
our Premium Content:  News alerts, weekly reports and conference planners
BIOMARKER:

U2AF1 mutation

i
Other names: U2AF1, U2 Small Nuclear RNA Auxiliary Factor 1, U2(RNU2) Small Nuclear RNA Auxiliary Factor Binding Protein, U2 SnRNP Auxiliary Factor Small Subunit, Splicing Factor U2AF 35 KDa Subunit, U2AFBP, U2AF35, U2 Small Nuclear Ribonucleoprotein Auxillary Factor, 35-KD Subunit, U2(RNU2) Small Nuclear RNA Auxiliary Factor 1, U2 Small Nuclear RNA Auxillary Factor 1, Splicing Factor U2AF 35kDa Subunit, U2 Auxiliary Factor 35 KDa Subunit, RNU2AF1, FP793, RN
Entrez ID:
Related biomarkers:
1d
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.
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
3d
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.
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)
7d
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
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)
11d
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
17d
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.
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
20d
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.
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
29d
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
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 • 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
1m
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
Trial primary completion date
|
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 • U2AF1 mutation
|
ceralasertib (AZD6738)
1m
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.
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
1m
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.
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
2ms
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.
Journal
|
U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)
|
U2AF1 mutation • U2AF1 S34F
2ms
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.
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
2ms
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.
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
2ms
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.
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
2ms
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.
Journal
|
JAK2 (Janus kinase 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CALR (Calreticulin)
|
U2AF1 mutation • U2AF1 S34F
2ms
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.
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
3ms
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
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
3ms
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.
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
3ms
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.
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
3ms
Trial completion date • Trial primary completion date
|
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) • STAG2 (Stromal Antigen 2) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
Chr del(11q) • U2AF1 mutation • Chr del(7q)
|
Vyxeos (cytarabine/daunorubicin liposomal formulation) • pomalidomide
4ms
Genetic Characteristics of Patients with Young-Onset Myelodysplastic Neoplasms. (PubMed, J Clin Med)
In conclusion, a germline predisposition to myeloid neoplasms occurred in ~16% of young-onset MDS patients and was largely associated with primary immunodeficiencies, including GATA2 deficiency. Furthermore, the high frequency of somatic U2AF1 mutations in patients with young-onset MDS suggests the presence of a distinct MDS subtype.
Journal
|
U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)
|
U2AF1 mutation • U2AF1 S34F
4ms
Performance of the OncoUrine test on predicting patients who can avoid Re-TURBT and prognosis: A prospective, multicenter clinical study. (ASCO-GU 2024)
OncoUrine test after initial TURBT for NMIBC showed promise as to guide patient selection for Re-TURBT and risk stratification in the management of NMIBC. Clinical trial information: NCT05112523.
Clinical
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR3 (Fibroblast growth factor receptor 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • TERT (Telomerase Reverse Transcriptase) • ERCC2 (Excision repair cross-complementation group 2) • KDM6A (Lysine Demethylase 6A) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • ONECUT2 (One Cut Homeobox 2)
|
TP53 mutation • KRAS mutation • PIK3CA mutation • HER-2 mutation • HRAS mutation • U2AF1 mutation • ERBB3 mutation • TERT mutation
4ms
Global analysis of binding sites of U2AF1 and ZRSR2 reveals RNA elements required for mutually exclusive splicing by the U2- and U12-type spliceosome. (PubMed, Nucleic Acids Res)
The class switch of introns by a single mutation and the bias against G at the -1 position of U12-type 5' splice site support the notion that the identities of nucleotides in exonic regions adjacent to splice sites are fine-tuned to avoid recognition by the U2-type spliceosome. These findings may shed light on the mechanism of selectivity in U12-type intron splicing and the mutations that affect splicing.
Journal
|
U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
U2AF1 mutation
4ms
Mesothelioma in situ of the peritoneum: report of three cases and review of the literature. (PubMed, Histopathology)
This work describes the histologic features and clinicopathologic characteristics of peritoneal MIS in three cases, highlights BAP1 somatic and germline mutations in peritoneal MIS, and strengthens the importance of ancillary studies (including immunohistochemical and molecular studies) in the diagnosis of MIS.
Review • Journal • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • BRCA (Breast cancer early onset) • SMO (Smoothened Frizzled Class Receptor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit)
|
TET2 mutation • BAP1 mutation • U2AF1 mutation • SMO mutation
5ms
Interactions between Iron Overload, Oxidative Stress, and Somatic Mutations in Myelodysplastic Syndromes; Evidence from the Literature (ASH 2023)
Of 31 mutations found in the IPSS-M, an additional four mutations found in familial predisposing conditions (DDX41, GATA2, CHEK2, SAMD9) were searched as was TET2, for a total of 35 mutations. Fifty-four references were identified. Fifty-three references were preclinical/translational in nature, with one case report (WT1).
Oxidative stress
|
TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • WT1 (WT1 Transcription Factor) • CHEK2 (Checkpoint kinase 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • ERFE (Erythroferrone)
|
TP53 mutation • NRAS mutation • TET2 mutation • SF3B1 mutation • CBL mutation • CHEK2 mutation • U2AF1 mutation • STAG2 mutation
5ms
Analysis of Clinical Features, Prognostic Characteristics and Gene Mutations of the EB Subtype of Primary Myelodysplastic Syndrome Patients with Myelofibrosis (ASH 2023)
MDS-MF has unique laboratory and clinical characteristics, act as an independent risk factor for shorter OS and worse PFS in the MDS-MF patients in our large cohort. In this study, we retrospectively analyzed 417 primary MDS cases in our hospital and analyzed the impact of MF on MDS-EB group and MDS-Non-EB group respectively. Our results showed the MF has a worse OS on the MDS-EB-MF group than the MDS-EB-MF0 group but no impact on MDS-Non-EB cohort.
Clinical
|
TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • WT1 (WT1 Transcription Factor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • GATA2 (GATA Binding Protein 2) • CRP (C-reactive protein)
|
U2AF1 mutation
5ms
Co-Mutational Patterns with BCOR Influences Biological Characteristics and Clinical Outcomes of Myeloid Neoplasms (ASH 2023)
Furthermore, patients with BCORMT, ASXL1MT, and concomitant DNA methylation-related gene mutations had worse outcomes compared to those with concomitant spliceosome mutation and BCORWT. Our findings suggest that co-mutational patterns of BCOR may further clarify diagnosis and classification schemes, highlighting potential synergies among subcategories of gene mutations and their prognostic value.
Clinical • Clinical data
|
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) • BCL6 (B-cell CLL/lymphoma 6) • 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) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
NPM1 mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation • U2AF1 mutation • BCOR mutation
5ms
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).
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
5ms
First Time Mexican Report of Next Gene Sequencing (NGS) Panel in Newly Diagnose Acute Myeloid Leukemia (AML). Series of Cases (ASH 2023)
Total of 47 patients, male: 29 (61%,) female: 18 (38. 3%). From de 47 patients, 39 were de novo AML (83%) and 8 patients secondary (17%)Morfología Classification of AML MO: 1 patient 2.
Clinical • Next-generation sequencing
|
KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • NOTCH1 (Notch 1) • NF1 (Neurofibromin 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) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • BCOR (BCL6 Corepressor) • CSF3R (Colony Stimulating Factor 3 Receptor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • PHF6 (PHD Finger Protein 6) • CALR (Calreticulin) • GATA1 (GATA Binding Protein 1) • ETNK1 (Ethanolamine Kinase 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • ANKRD26 (Ankyrin Repeat Domain Containing 26)
|
KRAS mutation • U2AF1 mutation
5ms
Concordance/Discordance of Paired Sequencing of Bone Marrow Tissue and Myeloid Sarcoma Samples- a Meta-Analysis (ASH 2023)
Discordant mutations are commonly seen in myeloid sarcoma when compared with paired bone marrow biopsy samples. NPM1 mutation discordance was the most enriched in the MS sample, followed by TP53. Discordance was associated with non-skin/soft tissue sites.
Retrospective data • Discordant
|
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)
|
TP53 mutation • NPM1 mutation • U2AF1 mutation
5ms
Next Generation Sequencing and Cytogenetics in Acute Myeloid Leukemia - Therapeutic and Prognostic Impact: A Retrospective Cohort from a Private Centre of Reference in Latin America (ASH 2023)
Next-Generation Sequencing, combined with cytogenetic analysis, has improved precision in prognosis prediction of AML patients of each patient, allowing safe implementation of appropriate individualized therapy. This study showed and association between high-risk cytogenetics and worse prognosis in AML, but no association was observed between molecular risk and AML morbimortality. Further studies with a bigger population and longer follow-up should be conducted in Latin America in order to better clarify and delve deeper into the results reported in this cohort.
Retrospective data • Next-generation sequencing
|
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • 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) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
TP53 mutation • ASXL1 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation
5ms
Lessons of Nature in Trisomy-8 MDS and AML: Determinants of Clonal Drive (ASH 2023)
8 itself. Indeed, we found transcriptomic changes pertinent to +8 MDS whose role in driving leukemogenesis and interaction with specific myeloid drivers needs to be confirmed by future experimentations on cellular and murine models.
IO biomarker
|
FLT3 (Fms-related tyrosine kinase 3) • 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) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • BAG4 (BAG Cochaperone 4) • PVT1 (Pvt1 Oncogene) • LY96 (Lymphocyte Antigen 96)
|
FLT3 mutation • DNMT3A mutation • RUNX1 mutation • U2AF1 mutation • STAG2 mutation
5ms
The Prevalence and Mutational Spectrum of Clonal Hematopoiesis in Diverse Populations in New York City (ASH 2023)
Leveraging population genetic-based inference of ancestry groups, we have demonstrated for the first time that different ancestries residing in NYC have a different risk and pattern of CH somatic mutations. In particular, we demonstrate that non-Jewish Europeans have lower risk of CH compared to all other groups, and Dominicans in particular have a significantly higher risk. Understanding the relative rates of CH across ancestries and their association with chronic diseases such as CVD and cancer will further refine recommendations directed towards lifestyle modifications and rational therapeutics that prevent the progression of CH & associated comorbidities.
Clinical
|
DNMT3A (DNA methyltransferase 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) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • PRPF8 (Pre-MRNA Processing Factor 8)
|
DNMT3A mutation • ASXL1 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation
5ms
Dysregulated Alternative Splicing in Inv(16) Acute Myeloid Leukemia Via U2AF1 Deacetylation during DNA Damage Response (ASH 2023)
7299). Altogether, these studies reveal mechanistic insights into DNA damage induced regulation of post-translational acetylation of U2AF1 splicing factor and provide a mechanistic link to the dysregulated alternative splicing and impaired DNA damage response in inv(16) AML.
BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • BCLAF1 (BCL2 Associated Transcription Factor 1)
|
U2AF1 mutation
5ms
NGS Profile and the Mathematical Prediction Model for Venetoclax Combination Therapy in HM-Screen-Japan 02 Study (ASH 2023)
Introduction Azacitidine and venetoclax combination therapy (Aza/Ven) is a novel strategy for acute myeloid leukemia (AML). Our mathematical model, involving gene mutations and WT1, could efficiently predict the response of Aza/Ven, which may support the selection of 1 st line treatment. In conclusion, our study revealed the genetic landscape of real-world Aza/Ven therapy and provided a potential prognostic model.
Combination therapy • Next-generation sequencing
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • 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) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • 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 • IDH2 mutation • NPM1 mutation • RUNX1 mutation • ASXL1 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • CEBPA mutation • STAG2 mutation • WT1 mutation • ZRSR2 mutation
|
Venclexta (venetoclax) • azacitidine
5ms
Genomic Analyses Unveil the Pathogenesis and Inform on Therapeutic Targeting in KMT2A-PTD AML (ASH 2023)
Given the results obtained with menin inhibitors in KMT2A-rearranged and NPM1-mutated AML, our findings open an opportunity for exploiting a therapeutic vulnerability in all HOX-AML including KMT2A-PTD AML or AML with high MEN1 expression. Since HOX-AML highly express genes according to the HOX differentiation profile, stage-specific surface proteins coded by these genes would be promising targets.
Genomic analysis
|
FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD276 (CD276 Molecule) • SRSF2 (Serine and arginine rich splicing factor 2) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • PML (Promyelocytic Leukemia) • CD34 (CD34 molecule) • STAG2 (Stromal Antigen 2) • CD14 (CD14 Molecule) • LILRB4 (Leukocyte Immunoglobulin Like Receptor B4) • MEN1 (Menin 1) • CD1D (CD1d Molecule) • CD86 (CD86 Molecule) • HOXB2 (Homeobox B2) • NKX2-3 (NK2 Homeobox 3)
|
NPM1 mutation • TET2 mutation • KMT2A rearrangement • MLL rearrangement • SRSF2 mutation • U2AF1 mutation • STAG2 mutation • MLL mutation • MLL translocation • KMT2A expression • KMT2A-PTD • CD1D expression