News - ETV6 mutation - LARVOL VERI

3ms

Short-term Effect of Venetoclax Combined with Azacitidine and "7+3" Regimen in the Treatment of Newly Diagnosed Elder Patients with Acute Myeloid Leukemia (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

The short-term effect of VEN+AZA group and "7+3" regimens in eldrly AML patients are similar， but the VEN+AZA regimen had a lower incidence of infection. The presence of chromosome 7 abnormality（7q-/-7） may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.

3 months ago

Journal

ETV6 (ETS Variant Transcription Factor 6)

ETV6 mutation

Venclexta (venetoclax) • azacitidine

4ms

The genetic and immune features of salivary gland secretory carcinoma with high-grade transformation. (PubMed, Oral Dis)

Our findings reveal novel gene alterations involved in the progression of HGT in SCs. Most HGT SCs patients cannot benefit from PD-L1 blocking and may be approached with a distinct treatment strategy including the lymph node dissection and application of molecular target drugs in precision oncology.

4 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

RET (Ret Proto-Oncogene) • ARID1A (AT-rich interaction domain 1A) • NRG1 (Neuregulin 1) • CD8 (cluster of differentiation 8) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • NOTCH3 (Notch Receptor 3) • GATA6 (GATA Binding Protein 6)

PD-L1 expression • ARID1A mutation • RET mutation • NOTCH3 mutation • MLL mutation • ETV6 mutation

4ms

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.

4 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

6ms

Genomic Correlates of Radiosensitivity in Diffuse Large B Cell Lymphoma (ASH 2023)

Its role in DLBCL is not well defined, with preclinical studies suggesting a distinct role compared to leukemias. Due to the limited sample size, these findings are hypothesis generating and warrant further study with larger, prospective cohorts to validate the ability of genomic signatures to predict RT response.

6 months ago

TP53 (Tumor protein P53) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • ETV6 (ETS Variant Transcription Factor 6) • KMT2D (Lysine Methyltransferase 2D) • TNFAIP3 (TNF Alpha Induced Protein 3) • PIM1 (Pim-1 Proto-Oncogene)

ETV6 mutation

MSK-IMPACT

7ms

Single-Cell Genomics and Proteomics Reveals Venetoclax-Resistant Monocytic Differentiation of TP53 LOH Clones in TP53 Mutant AML (ASH 2023)

Patients 1 and 3 received treatment with CD47AB (Magrolimab), 5'-Azacitidine (Aza), and Venetoclax (Ven); Patient 2 received IMGN632 (CD123-targeting ADC), Aza and Ven. Patient 4 received p97 Inhibitor CB-5339; Patient 5 received CD47 inhibitor (ALX148), Aza, Ven... This study establishes a genotype-phenotype connection through single-cell proteogenomic profiling of TP53-mutated AML, describing the clonal evolution and immunophenotypic dynamics during treatment while proposing a potential mechanism of resistance.

7 months ago

IO biomarker

TP53 (Tumor protein P53) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CD8 (cluster of differentiation 8) • ETV6 (ETS Variant Transcription Factor 6) • BCL2L1 (BCL2-like 1) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • CD34 (CD34 molecule) • CD36 (thrombospondin receptor) • CD14 (CD14 Molecule) • CD68 (CD68 Molecule) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • ITGAM (Integrin, alpha M) • IL3RA (Interleukin 3 Receptor Subunit Alpha)

TP53 mutation • IDH1 R132 • ETV6 mutation • IDH1 R132L

Venclexta (venetoclax) • azacitidine • magrolimab (ONO-7913) • evorpacept (ALX148) • pivekimab sunirine (IMGN632) • CB-5339

7ms

Influence of Co-Mutational Patterns in Disease Phenotype and Clinical Outcomes of Chronic Myelomonocytic Leukemia (ASH 2023)

These data suggest that somatic mutations in CMML have unique patterns of clustering that define disease phenotype and influence disease outcomes.

7 months ago

Clinical • Clinical data

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • 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) • ETV6 (ETS Variant Transcription Factor 6) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • SETBP1 (SET Binding Protein 1) • BCORL1 (BCL6 Corepressor Like 1)

TP53 mutation • BRAF mutation • NRAS mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation • EZH2 mutation • CBL mutation • SRSF2 mutation • U2AF1 mutation • CEBPA mutation • WT1 mutation • Chr del(7q) • ETV6 mutation

7ms

Impact of Mutational Status on Clinical Response to Imetelstat in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Phase 3 Study (ASH 2023)

Higher RBC-TI rates were observed in patients with various baseline mutational profiles treated with imetelstat compared with placebo in IMerge. While the sample size for specific mutations was small, consistent with the observation that patients with LR-MDS have a low number of specific mutations, TI responses in patients receiving imetelstat occurred regardless of the presence of mutations associated with poor prognosis or the number of mutations. Imetelstat showed comparable TI rates across different molecularly defined subgroups, suggesting that clinical benefit of imetelstat in patients with LR-MDS is independent of the underlying molecular pattern.

7 months ago

Clinical • P3 data

TP53 (Tumor protein P53) • 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) • ETV6 (ETS Variant Transcription Factor 6) • CUX1 (cut like homeobox 1)

TP53 mutation • DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation • SF3B1 K700E • ETV6 mutation • CUX1 mutation

imetelstat (GRN163L)

7ms

TL-895, a Highly Selective, Covalent Inhibitor of Bruton's Tyrosine Kinase (BTK), Sensitizes Myeloproliferative Neoplasm (MPN)-Blast Phase Stem Cells to Navtemadlin By Targeting Intrinsic Dysregulated MDM2/p53 and NF-Κb Pathways and Disrupting the Protective Tumor Microenvironment (TME) (ASH 2023)

Our results indicate that BTKi therapy might increase susceptibility of MPN-BP SC to MDM2i therapy, by upregulating p53 activity and dampening NF-κB signaling, and also by disrupting protective TME interactions that sustain MPN-BP SC. This novel combination merits further clinical investigation in advanced phase MPN.

7 months ago

IO biomarker

KRAS (KRAS proto-oncogene GTPase) • MDM2 (E3 ubiquitin protein ligase) • ETV6 (ETS Variant Transcription Factor 6) • BCL2L1 (BCL2-like 1) • WT1 (WT1 Transcription Factor) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • CDK1 (Cyclin-dependent kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DDB2 (Damage Specific DNA Binding Protein 2) • ATF3 (Activating Transcription Factor 3) • BTG2 (BTG Anti-Proliferation Factor 2)

KRAS mutation • TP53 wild-type • WT1 mutation • ETV6 mutation

navtemadlin (KRT-232) • M7583

7ms

Familial Thrombocytopenia-Associated Germline ETV6 P214L Mutation Results in XPO1-Mediated Nuclear Export (ASH 2023)

We developed a mouse model that recapitulates this export signal in the endogenous ETV6 allele and found that this model demonstrates a thrombocytopenic phenotype as seen in human patients. Reductions in HSCs and MkPs suggest both a decreased fitness of HSCs, as well as dysregulated megakaryopoiesis in this model.

7 months ago

IO biomarker

ETV6 (ETS Variant Transcription Factor 6) • XPO1 (Exportin 1)

ETV6 mutation

8ms

Macrofollicular Architecture in Invasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Pitfall in Thyroid Practice. (PubMed, Head Neck Pathol)

Macrofollicular architecture in invasive encapsulated follicular variant of papillary thyroid carcinoma is a major pitfall in thyroid oncology practice. Long-standing disease, and ultrasonographic and cytological features that overlap with benign disease, often lead to underdiagnosis during pre-operative evaluation. As patients may consequently develop distant metastases and have inadequate treatment response, there is a need for more vigilant understanding of the spectrum of macrofollicular thyroid disease for accurate diagnosis. ETV6::NTRK3 or other fusions, when found, present opportunities for targeted therapy.

8 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RET (Ret Proto-Oncogene) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • ETV6 (ETS Variant Transcription Factor 6)

BRAF V600E • NRAS mutation • BRAF V600 • NTRK3 fusion • RET fusion • HRAS mutation • ETV6 mutation

8ms

PAPILLARY THYROID CANCERS WITH NTRK FUSION MUTATIONS: BENIGN CYTOLOGIC APPEARANCE AND CLINICALLY AGGRESSIVE DISEASE (ATA 2023)

Although rare, NTRK fusion mutations are now recognized in 5‐6% of adults with PTC. Tumors with this mutation had a high likelihood of multifocality, extrathyroidal extension, vascular invasion, lymph node metastases, and distant metastases.

8 months ago

Clinical

NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase)

NTRK3 fusion • ETV6-NTRK3 fusion • ETV6 mutation • NTRK fusion

10ms

Next Generation Sequencing (NGS) in Familial Acute Myeloid Leukemia and Myelodisplastic Syndromes (clinicaltrials.gov)

P=N/A, N=20, Recruiting, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

10 months ago

Trial completion date • Trial primary completion date

TERT (Telomerase Reverse Transcriptase) • RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • GATA2 (GATA Binding Protein 2) • ANKRD26 (Ankyrin Repeat Domain Containing 26)

ETV6 mutation

10ms

The clinical and molecular spectrum of ETV6 mutated myeloid neoplasms. (PubMed, Br J Haematol)

The median OS of the cohort was 17.5 months. This report highlights the clinical and molecular associations of somatic ETV6 mutations in myeloid neoplasms, suggests their occurrence as a later event, and proposes further translational research questions for their role in myeloid neoplasia.

10 months ago

Journal

RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • ETV6 (ETS Variant Transcription Factor 6) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • SETBP1 (SET Binding Protein 1)

ASXL1 mutation • U2AF1 mutation • ETV6 mutation

1year

GENOMIC AND TRANSCRIPTOMIC PROFILING REVEALS NOVEL GENE FUSIONS AND MARKERS OF CLINICAL RESPONSE IN PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2023)

With novel gene fusions and uncovered associations between the dynamics of MRD decline, TP53 and RUNX1 high burden mutations in this real-world cohort, our dataset provides valuable, clinically relevant insights to the genomic and transcriptomic landscape of children diagnosed with ALL. Pediatric, ALL, Prognosis, Mutation analysis

1 year ago

Clinical

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) • PTEN (Phosphatase and tensin homolog) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • CRLF2 (Cytokine Receptor Like Factor 2) • IKZF1 (IKAROS Family Zinc Finger 1) • WT1 (WT1 Transcription Factor) • NT5C2 (5'-Nucleotidase Cytosolic II) • PAX5 (Paired Box 5) • TCF3 (Transcription Factor 3) • P2RY8 (P2Y Receptor Family Member 8) • PBX1 (PBX Homeobox 1) • CCND3 (Cyclin D3) • PHF6 (PHD Finger Protein 6)

TP53 mutation • BCR-ABL1 fusion • RUNX1 mutation • IKZF1 deletion • WT1 mutation • NT5C2 mutation • ETV6 mutation • NT5C mutation • PAX5 fusion • ABL1 deletion

TruSight RNA Pan-Cancer Panel

1year

ASSOCIATION OF GENE MUTATIONS AND CLINICAL MANIFESTATIONS AND PROGNOSIS IN THE CLINICAL COHORT WITH 218 MDS PATIENTS (EHA 2023)

Our MDS cohort study showed that the patients with older age, higher score of IPSS-R, presence of mutations in gene TP53 、 DNMT3A 、 SRSF2 、 STAG2 have a poor prognosis. Older age 、 TP53 and IPSS-R are independent prognostic factors. The survival of patients with very low/low risk IPSS-R score patients and ETV6 or TP53 or DNMT3A mutation is similar with that with very high risk of IPSS-R score.

1 year ago

Clinical

TP53 mutation • DNMT3A mutation • TET2 mutation • SRSF2 mutation • U2AF1 mutation • STAG2 mutation • ETV6 mutation

1year

PHARMACOLOGICAL EZRIN INHIBITION REDUCES GROWTH, ADHESION, MIGRATION AND REGULATE GENE RELATED TO APOPTOSIS AND CELL CYCLE IN ACUTE LYMPHOBLASTIC LEUKAEMIA (EHA 2023)

Downregulation of genes related to cell cycle progression (CCNA2 and CCNB1) and anti-apoptotic response (BCL2), and upregulation of genes related to cell cycle arrest (CDKN1A, CDKN1B), pro-apoptotic (BAX) response,support the hypothesis that NSC305787 treatment reduces viability by inducing apoptosis. Our results indicate that the ezrin inhibitor, NSC305787, has antileukemic effects in ALL, including reduction of viability and clonogenicity, anti-invasive effects, and regulation of pathways involved in protein synthesis. Supported by CNPq, CAPES and FAPESP.

1 year ago

PARP Biomarker • IO biomarker

PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • RUNX1 (RUNX Family Transcription Factor 1) • MCL1 (Myeloid cell leukemia 1) • ETV6 (ETS Variant Transcription Factor 6) • BCL2L1 (BCL2-like 1) • CXCL12 (C-X-C Motif Chemokine Ligand 12) • CCNA2 (Cyclin A2) • EBF1 (EBF Transcription Factor 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • CCNB1 (Cyclin B1)

ETV6 mutation

NSC305787

1year

MORE: A Pilot Study to Evaluate the Feasibility of Post-Hematopoietic Stem Cell Transplant Prophylaxis With Decitabine Combined With Filgrastim for Children and Young Adults With AML, MDS and Related Myeloid Malignancies (clinicaltrials.gov)

P2, N=37, Recruiting, Franziska Wachter | Not yet recruiting --> Recruiting

1 year ago

Enrollment open

RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • ANKRD26 (Ankyrin Repeat Domain Containing 26)

RUNX1 mutation • DDX41 mutation • GATA2 mutation • ETV6 mutation

decitabine • Neupogen (filgrastim)

1year

P2, N=37, Not yet recruiting, Franziska Wachter

1 year ago

New P2 trial

RUNX1 mutation • DDX41 mutation • GATA2 mutation • ETV6 mutation

decitabine • Neupogen (filgrastim)