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ZRSR2 mutation
i
Other names: ZRSR2, Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2, U2AF1-RS2, URP, U2(RNU2) Small Nuclear RNA Auxiliary Factor 1-Like 2, U2AF1L2, ZC3H22, U2 Small Nuclear Ribonucleoprotein Auxiliary Factor 35 KDa Subunit-Related Protein 2, Renal Carcinoma Antigen NY-REN-20, U2AF35-Related Protein, U2AF1RS2, CCCH Type Zinc Finger, RNA-Binding Motif And Serine/Arginine Rich Protein 2, Zinc Finger (CCCH Type), RNA Binding Motif And Serine/Arginine Rich 2, U2 Small Nuclear Ribonucleoprotein Auxiliary Factor, Small Subunit 2, U2 Small Nuclear RNA Auxiliary Factor 1-Like 2
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Entrez ID:
8d
Validation of the Revised 2022 European LeukemiaNet Risk Stratification in Adult Patients with Acute Myeloid Leukemia. (PubMed, Blood Adv)
We aimed to validate the prognostic value of the 2022 ELN classification (ELN22) evaluating 1,570 newly diagnosed AML patients (median age, 56 years) treated with cytarabine-based intensive chemotherapy regimens...In conclusion, the ELN22 risk stratification improves prognostic discrimination in a large cohort of intensively treated AML patients. Given the heterogeneous outcome in patients with MR gene alterations, ranging between those of intermediate and adverse risk patients, we suggest reevaluation of risk allocation in these patients.
Journal
|
TP53 (Tumor protein P53) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • STAG2 (Stromal Antigen 2) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
TP53 mutation • EZH2 mutation • STAG2 mutation • ZRSR2 mutation
|
cytarabine
2ms
Characterisation and prognostic impact Of ZRSR2 mutations in myeloid neoplasms. (PubMed, Leukemia)
No abstract available
Journal
|
ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
ZRSR2 mutation
7ms
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
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cytarabine • Pemazyre (pemigatinib) • daunorubicin • Starasid (cytarabine ocfosfate)
10ms
Minor Introns Impact on Hematopoietic Malignancies. (PubMed, Exp Hematol)
Recent technological advancements have uncovered insights into minor introns, raising inquiries beyond current understanding. This review comprehensively explores the importance of minor intron regulation, the molecular implications of minor (U12-type) spliceosomal mutations and cis-regulatory regions, and the evolutionary progress of studies on minor, aiming to provide a sophisticated understanding of their intricate role in cancer biology.
Journal
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ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • LZTR1 (Leucine Zipper Like Transcription Regulator 1)
|
ZRSR2 mutation
12ms
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
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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
1year
Acute Myeloid Leukemia (AML) Patients with Myelodysplasia (MDS) Related-Gene Mutations in First Complete Remission (CR1) Found to Have Benefit from Allogeneic Hematopoietic Stem Cell Transplant (HCT) (ASH 2023)
In our cohort of 1228 AML patients, we have identified 278 AML patients with myelodysplasia-related gene mutations (22.6%). We have confirmed that allogeneic HCT in CR1 is strongly recommended in a subgroup of AML with myelodysplasia-related gene mutations based on the favorable impact of HCT in CR1 on RFS from the present study. This result supports the urgent referral of this patient group for allogeneic HCT in CR1.
Clinical
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • 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) • 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)
|
IDH1 mutation • NPM1 mutation • ASXL1 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • STAG2 mutation • ZRSR2 mutation
1year
Cardiovascular Risk Factors Are Common in Myeloproliferative Neoplasms and Portend Worse Survival and Thrombotic Outcomes (ASH 2023)
Our cohort contained 399 (39.6%) ET, 312 (31.0%) PV, and 237 (23.5%) MF or pre-fibrotic MF patients. The median age at diagnosis was 58.5 years, and 47.9% of patients were male. The overall prevalence of hyperlipidemia, hypertension, and diabetes at MPN diagnosis was 16%, 20%, and 8%.
Clinical
|
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) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CALR (Calreticulin) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
ASXL1 mutation • SRSF2 mutation • U2AF1 mutation • ZRSR2 mutation
1year
Error-Corrected Next-Generation Sequencing Provides a Comprehensive Overview of the Subclonal Mutation Landscape and Its Prognostic Implications in Juvenile Myelomonocytic Leukemia (ASH 2023)
We successfully performed error-corrected NGS to assess comprehensive subclonal secondary mutational profiles, including very low VAF variants. The presence of subclonal mutations, particularly in RAS pathway genes, was associated with poor OS. These findings provide important information for appropriate risk stratification, which will contribute to the implementation of precision medicine for patients with JMML.
Next-generation sequencing
|
KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • ASXL1 (ASXL Transcriptional Regulator 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • JAK3 (Janus Kinase 3) • SETBP1 (SET Binding Protein 1) • SH2B3 (SH2B Adaptor Protein 3) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
KRAS mutation • RAS mutation • CBL mutation • JAK3 mutation • ZRSR2 mutation
1year
Clinical Factors but Not Somatic Mutations Predict for Survival in Patients with Myelofibrosis Undergoing Allogeneic Hematopoietic Cell Transplant: Analysis of the North American Myelofibrosis Transplant Outcome (NAMTO) Study (ASH 2023)
Interestingly, using alternative donors (MMURD and haplo identical) didn't have a negative effect on OS, possibly reflecting the use of post-transplant cyclophosphamide for GVHD prophylaxis in recent years. In this large multicenter analysis only clinical variables; hemoglobin and platelets, were found to be associated with OS after allo-HCT in MF patients. Somatic mutations associated with poor prognosis were not associated with OS suggesting that transplant can overcome their negative impact. Splenomegaly was associated with delayed engraftment but not OS.
Clinical
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • 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) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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ASXL1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • ZRSR2 mutation
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cyclophosphamide
1year
Clinical Outcomes and Mutational Profile Associated with Dysmyelopoiesis in Chronic Myelomonocytic Leukemia (ASH 2023)
In addition, both dysgranulopoiesis and dysmegakaryopoiesis have demonstrated a negative prognostic impact on the survival of patients in our series that was not captured by the CPSS and Mayo prognostic model. Their worse prognosis could be partially justified by their association with poor prognostic mutations (e.g. NRAS, ASXL1, TP53), which allows us to visualize them as a good surrogate of poor prognostic molecular profiles.
Clinical • Clinical data
|
TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SETBP1 (SET Binding Protein 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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TP53 mutation • NRAS mutation • ASXL1 mutation • TET2 mutation • ZRSR2 mutation
1year
Pre-Transplant Somatic Co-Occurring Mutations (by next generation sequencing) in Acute Myeloid Leukemia: Frequency and Impact on Clinical Outcomes after Allogeneic Hematopoietic Cell Transplantation - a Large Study on Behalf of the EBMT Acute Leukemia Working Party (ASH 2023)
NGS at diagnosis can be extremely useful in risk stratification of AML patients undergoing allo-HSCT, potentially allowing adequate post-transplant interventions. Notably, the 2-year LFS of 70% for patients harboring RUNX1 and/or ASXL1 and/or SRSF2 mutation indicates that allo-HSCT can overcome the adverse risk associated with these somatic mutations at diagnosis.
Clinical • Clinical data • Next-generation sequencing • Pre-transplantation
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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) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • 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 • FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • ASXL1 mutation • SRSF2 mutation • U2AF1 mutation • CEBPA mutation • STAG2 mutation • FLT3 wild-type • ERBB4 mutation • ZRSR2 mutation
1year
E7820, an Anti-Cancer Sulfonamide, in Combination with Venetoclax in Patients with Splicing Factor Mutant Myeloid Malignancies: A Phase II Clinical Trial (ASH 2023)
Secondary endpoints include overall and event-free survival. Correlative biomarker and pharmacodynamic parameters will be assessed as exploratory endpoints including effects on RBM39 protein levels, changes in global and key target splicing events, and evaluation of DCAF15 mRNA levels and response to therapy.
Clinical • P2 data • Combination therapy • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • SF3B1 (Splicing Factor 3b Subunit 1) • MCL1 (Myeloid cell leukemia 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)
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SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • MCL1 expression • ZRSR2 mutation
|
Venclexta (venetoclax) • E7820
over1year
Clinical and prognostic profile of SRSF2 and related spliceosome mutations in patients with acute myeloid leukemia. (PubMed, Mol Biol Rep)
SF mutation is a distinct subgroup of AML frequently associated with clinic-biological features and poor outcome. SRSF2 could be potential targets for novel treatment in AML.
Journal
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • SRSF2 (Serine and arginine rich splicing factor 2) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
IDH2 mutation • KIT mutation • SRSF2 mutation • ZRSR2 mutation
over1year
A Study of E7820 in People With Bone Marrow (Myeloid) Cancers (clinicaltrials.gov)
P2, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2023 --> Aug 2024 | Trial primary completion date: Aug 2023 --> Aug 2024
Trial completion date • Trial primary completion date
|
FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • 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)
|
IDH2 mutation • FLT3 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • ZRSR2 mutation
|
E7820
over1year
VALIDATION OF THE REVISED 2022 EUROPEAN LEUKEMIANET (ELN) RISK STRATIFICATION IN ADULT PATIENTS WITH ACUTE MYELOID LEUKEMIA (EHA 2023)
In conclusion, the novel ELN22 risk stratification improves prognostic discrimination in a large cohort of intensively treated AML pts. Given the heterogeneous outcome in pts with MR gene mutations, ranging between those of intermediate- and adverse-risk pts, we suggest reevaluation of risk allocation in these patients. AML
Clinical
|
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • 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) • 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 • NPM1 mutation • RUNX1 mutation • ASXL1 mutation • U2AF1 mutation • CEBPA mutation • STAG2 mutation • ZRSR2 mutation
over1year
A Study of E7820 in People With Bone Marrow (Myeloid) Cancers (clinicaltrials.gov)
P2, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=38 --> 12
Enrollment closed • Enrollment change
|
FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • 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)
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IDH2 mutation • FLT3 mutation • SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • ZRSR2 mutation
|
E7820
almost2years
FREQUENCY AND IMPACT OF PRE-TRANSPLANT SOMATIC MUTATIONS ON CLINICAL OUTCOMES OF AML PATIENTS RECEIVING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (EBMT 2023)
Next generation sequencing is a pivotal important too for risk stratification of patients with AML receiving allo-HSCT and determining post-transplant consolidation.
Clinical • Clinical data • Pre-transplantation
|
KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • 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) • GATA2 (GATA Binding Protein 2) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
TP53 mutation • KRAS mutation • NRAS mutation • FLT3 mutation • NPM1 mutation • KIT mutation • DNMT3A mutation • RUNX1 mutation • SRSF2 mutation • U2AF1 mutation • STAG2 mutation • ZRSR2 mutation
almost2years
FREQUENCY AND IMPACT OF PRE-TRANSPLANT SOMATIC CO-OCCURRING MUTATIONS ON CLINICAL OUTCOMES OF AML PATIENTS RECEIVING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: ON BEHALF OF THE EBMT ALWP (EBMT 2023)
NGS at diagnosis can be extremely useful in risk stratification of AML patients undergoing allo-HSCT, potentially allowing adequate post-transplant interventions.
Clinical • Clinical data • Pre-transplantation
|
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) • 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 • FLT3 mutation • NPM1 mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • SRSF2 mutation • U2AF1 mutation • STAG2 mutation • FLT3 wild-type • ZRSR2 mutation
almost2years
High BM plasma S100A8/A9 is associated with a perturbed microenvironment and poor prognosis in myelodysplastic syndromes. (PubMed, Blood Adv)
Lastly, through deep-sequenced transcriptomic analysis, we demonstrated that higher S100A8/A9 in the BM intimated a perturbed microenvironment with enhanced myeloid-derived suppressor cell-mediated tumor immune escape signal, altered metabolism, and impairment in the functions and quantities of CD8+ T cells and NK cells. S100A8/A9 in the BM microenvironment may be a potential biomarker in the prognostication of MDS and target for novel therapy.
Journal • IO biomarker
|
CD8 (cluster of differentiation 8) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • STAG2 (Stromal Antigen 2) • S100A8 (S100 Calcium Binding Protein A8) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
ASXL1 mutation • EZH2 mutation • STAG2 mutation • ZRSR2 mutation
almost2years
Significance of hypergammaglobulinemia in patients with chronic myelomonocytic leukemia. (PubMed, Wien Med Wochenschr)
Our results show that hypergammaglobulinemia is present in a proportion of CMML patients and that this abnormality is associated with poor overall survival. The role of chronic inflammation in the pathophysiology of CMML needs to be further investigated.
Journal
|
NRAS (Neuroblastoma RAS viral oncogene homolog) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
NRAS mutation • ZRSR2 mutation
almost2years
Genetic Landscape of BPDCN Arising in CML Remission (ASH 2022)
With initial therapy of dasatinib 100 mg, his disease status achieved complete molecular response (CMR) at 24 months of treatment; achieved CMR (MR 4.5) at 43 months...HyperCVAD/MA (cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and arabinocytocine) was selected as induction therapy...These facts suggest that the presence of mechanism is essential for the development of BPDCN other than driver mutation in ZRSR2. Further investigation of BPDCN with PCHM would provide useful information on the pathogenesis of BPDCN.
Clinical
|
ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD4 (CD4 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
ASXL1 mutation • TET2 mutation • CD123 positive • ZRSR2 mutation
|
dasatinib • doxorubicin hydrochloride • cyclophosphamide • methotrexate • vincristine
almost2years
Effect of Mutation Allele Frequency on the Risk Stratification of Myelodysplastic Syndrome Patients. (PubMed, Am J Hematol)
Furthermore, patients harboring U2AF1 mutation might benefit from hypomethylating agents. This study demonstrated the critical role of VAF of mutations for risk stratification in MDS patients and may be incorporated in novel scoring systems.
Journal
|
TP53 (Tumor protein P53) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • SETBP1 (SET Binding Protein 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
TP53 mutation • IDH2 mutation • DNMT3A mutation • ASXL1 mutation • TET2 mutation • EZH2 mutation • CBL mutation • U2AF1 mutation • ZRSR2 mutation
2years
A Phase II Clinical Trial of E7820 for Patients with Relapsed/Refractory Myeloid Malignancies with Mutations in Splicing Factor Genes (ASH 2022)
In this phase II trial of E7820 in AML and MDS patients with splicing factor mutations, we found acceptable safety of E7820 monotherapy at the previously established maximum tolerated dose. Although the efficacy of E7820 was limited, evidence of target engagement combined with the tolerability of RBM39 degradation serves as a proof of concept that splicing factor mutant disease can be targeted in humans. Combination therapies of E7820 with standard of care agents and the use of newer generation RBM39 degraders are in development.
Clinical • P2 data
|
SF3B1 (Splicing Factor 3b Subunit 1) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
SF3B1 mutation • SRSF2 mutation • U2AF1 mutation • ZRSR2 mutation
|
E7820
2years
Systematic Evaluation of AML-Associated Antigens Identifies Novel Anti-U5 snRNP200 Therapeutic Antibodies for the Treatment of AML (ASH 2022)
These data provide a high-density roadmap of the distribution of known and novel AML-associated antigens together with the Fc receptor distribution and immune microenvironment in AML. The results motivated discovery of a novel antibody-therapeutic targeting aberrant cell-surface U5 snRNP200 and research into mechanisms for cell surface trafficking of U5 snRNP200.
IO biomarker
|
NRAS (Neuroblastoma RAS viral oncogene homolog) • SF3B1 (Splicing Factor 3b Subunit 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD123 (Interleukin 3 Receptor Subunit Alpha) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IL2RA (Interleukin 2 receptor, alpha) • CD33 (CD33 Molecule) • CD70 (CD70 Molecule) • FCGR2A (Fc fragment of IgG receptor IIa) • THY1 (Thy-1 membrane glycoprotein) • CDK1 (Cyclin-dependent kinase 1) • FCGR2B (Fc Fragment Of IgG Receptor IIb) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
TET2 mutation • NRAS G12D • NRAS G12 • SF3B1 K700E • ZRSR2 mutation
2years
Effect of Mutation Allele Frequency on the Risk Stratification of Myelodysplastic Syndrome Patients (ASH 2022)
Conclusion We provide evidences that VAF is critical for risk stratification in MDS patients and should be considered in novel scoring systems. Our data fostered our understanding of the mutation burden of the diseases and provided future patient-tailored therapeutic avenues.
Clinical • Tumor mutational burden
|
TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • 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) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • SETBP1 (SET Binding Protein 1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
|
TP53 mutation • FLT3-ITD mutation • IDH2 mutation • FLT3 mutation • DNMT3A mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • CEBPA mutation • BCOR mutation • ZRSR2 mutation
|
TruSight Myeloid Sequencing Panel
2years
Prognostic Impact of Clonal Hierarchy of Myelodysplasia-Related Gene Mutations in AML Patients (ASH 2022)
In our study, 76% of MRG mutations occur in the dominant clone in newly diagnosed AML patients. Dominant MRG mutations have a worse prognosis compared to patients without MRG mutations, while prognosis of subclonal MRG mutations should be evaluated in larger cohorts. AML patients with subclonal TP53 mutation have a similar outcome to patients without TP53 mutation.
Clinical
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TP53 (Tumor protein P53) • 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)
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TP53 mutation • TP53 wild-type • ASXL1 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation • U2AF1 mutation • STAG2 mutation • ZRSR2 mutation
2years
Concurrent Zrsr2 mutation and Tet2 loss promote myelodysplastic neoplasm in mice. (PubMed, Leukemia)
Collectively, this study shows that concomitant Zrsr2 mutation and Tet2 loss are sufficient to initiate MDS in mice. Understanding this mechanistic interplay will be crucial for the identification of novel therapeutic targets in the spliceosome/epigenetic MDS subgroup.
Preclinical • Journal
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TET2 (Tet Methylcytosine Dioxygenase 2) • FOXM1 (Forkhead Box M1) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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TET2 mutation • ZRSR2 mutation
over2years
ZRSR2 AND TET2 MUTATIONS PROMOTE MDS BY DYSREGULATING GENE EXPRESSION AND ABERRANT ALTERNATIVE SPLICING IN MICE (EHA 2022)
Alternative splicing analysis identified the MAPK and the Fanconi Anemia pathway as key targets of aberrant splicing. All in all, gene expression dysregulation and aberrant mRNA splicing disturb important biological pathways and drive the molecular pathomechanism in Zrsr2 m/m Tet2 −/− mice.
Preclinical
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FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NOTCH1 (Notch 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • TLR7 (Toll Like Receptor 7) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2) • DUSP1 (Dual Specificity Phosphatase 1)
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TET2 mutation • ZRSR2 mutation
over2years
NONLINIEAR IMPACT OF CLINICAL FEATURES ON THE SURVIVAL OUTCOME OF MYELODYSPLASTIC SYNDROMES PATIENTS (EHA 2022)
This might be due to heterogeneity within the data set (e.g., 25% co-occurrence of SF3B1 with TP53 mutation) and needs to be investigated in larger cohorts. Conclusion We have established a nonlinear model that yields improved risk assessment compared to IPSS-R criteria.
Clinical
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TP53 (Tumor protein P53) • SF3B1 (Splicing Factor 3b Subunit 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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TP53 mutation • TET2 mutation • SF3B1 mutation • SRSF2 mutation • ZRSR2 mutation
over2years
Clonal cytopenia of undetermined significance and atypical Behçet's: the importance of zinc. (PubMed, BMJ Case Rep)
He was treated with oral zinc therapy and had resolution of recurrent oral ulcerations and significant reduction in severity of anal ulcerations. The functional impact of ZRSR2 mutation on spliceosome assembly is yet to be defined, but has been previously reported in CCUS with a clinical phenotype of macrocytic anaemia.
Journal
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ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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ZRSR2 mutation
over2years
Mutations in the ASXL1 and ZRSR2 genes are associated with the response to the combination of alvocidib and 5-azacytidine in higher-risk myelodysplastic syndromes (AACR 2022)
A phase 1b/2 study with Alv and 5-Aza or decitabine in higher-risk patients with MDS was recently completed (NCT03593915); however, biomarkers for response to the Alv and 5-Aza combination are not well characterized. ZRSR2 mutations also retained an independent impact on cell viability in multivariable analysis (p=0.035). Overall, we provide pre-clinical support for the use of 5-Aza+Alv combination for higher-risk MDS and identified ASXL1 and ZRSR2 mutations as potential genetic biomarkers of augmented response.
IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • ASXL1 (ASXL Transcriptional Regulator 1) • MCL1 (Myeloid cell leukemia 1) • CD34 (CD34 molecule) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)
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ASXL1 mutation • ZRSR2 mutation
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azacitidine • decitabine • alvocidib (DSP-2033)
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