News - EZH2 mutation - LARVOL VERI

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.

8 days ago

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

15d

Mandolin: A Study to Assess Efficacy and Safety of Oral Tazemetostat in Adult Participants With Relapsed/Refractory Follicular Lymphoma That Does Not Have an "EZH2 Gain-of-function" Genetic Mutation (clinicaltrials.gov)

P2, N=55, Not yet recruiting, Epizyme, Inc. | Trial completion date: Sep 2027 --> Apr 2029 | Trial primary completion date: Sep 2027 --> Apr 2029

15 days ago

Trial completion date • Trial primary completion date

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

EZH2 mutation • EZH2 wild-type

Tazverik (tazemetostat)

18d

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.

18 days 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

22d

ETCTN 10500: Testing the Safety of the Anti-cancer Drugs Tazemetostat and Belinostat in Patients With Lymphomas That Have Resisted Treatment (clinicaltrials.gov)

P1, N=64, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

22 days ago

Enrollment open

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

RAS wild-type • EZH2 mutation • EZH2 wild-type

Tazverik (tazemetostat) • Beleodaq (belinostat)

Complete response using the EZH2 inhibitor tazemetostat against multiple relapsed follicular lymphoma in the leukemic phase. (PubMed, Int Cancer Conf J)

Extended-interval dosing of tazemetostat transformed a partial response into a complete response. Thus, tazemetostat is effective for the treatment of multiple relapsed FL in the leukemic phase.

1 month ago

Journal

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

EZH2 mutation

Tazverik (tazemetostat)

Synergistic effect of concurrent high molecular risk mutations and lower JAK2 mutant variant allele frequencies on prognosis in patients with myelofibrosis-insights from a multicenter study. (PubMed, Leukemia)

Importantly, the integration of HMR/JAK2V617F VAF (≤50%) status significantly enhanced existing prognostic models, as evidenced by higher c-indexes and time-dependent ROC analyses. Single-cell studies with sequential follow-ups are warranted to decipher the clonal evolution of MF and how it relates to JAK2V617F VAF dynamics.

1 month ago

Clinical • Journal

JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2)

EZH2 mutation • SRSF2 mutation • JAK2 V617F • JAK2 mutation

Rare presentation and unconventional treatment of Rosai-Dorfman disease. (PubMed, BMJ Case Rep)

We present a case of a man in his late 50s with RDD who experienced worsening cytopenias, including severe neutropenia and respiratory distress, despite an initial positive response to steroids, rituximab and lenalidomide. Sirolimus was initiated and led to complete radiological remission of the disease. This case adds strength to the growing evidence supporting the efficacy of sirolimus in refractory RDD cases.

1 month ago

Journal

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • EZH2 mutation • KRAS G13 • KRAS G13C

Rituxan (rituximab) • lenalidomide • sirolimus

A Phase 1 Study of SHR2554 in Subjects With Relapsed or Refractory Mature Lymphoid Neoplasms (clinicaltrials.gov)

P1, N=272, Active, not recruiting, Jiangsu HengRui Medicine Co., Ltd. | Recruiting --> Active, not recruiting | Trial completion date: Aug 2023 --> Aug 2026 | Trial primary completion date: Feb 2023 --> Feb 2026

1 month ago

Enrollment closed • Trial completion date • Trial primary completion date

BCL2 (B-cell CLL/lymphoma 2) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • BCL6 (B-cell CLL/lymphoma 6)

EZH2 mutation

SHR-2554

2ms

EZH2 mutation is associated with the development of visceral metastasis by enhancing proliferation and invasion and inhibiting apoptosis in breast cancer cells. (PubMed, BMC Cancer)

EZH2 mutation is associated with VM development in breast cancer patients. The EZH2K515R mutation leads to VM and a poor prognosis by enhancing proliferation and invasion and inhibiting apoptosis in breast cancer cells.

2 months ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

BRCA2 mutation • BRCA1 mutation • EZH2 mutation • EZH2 wild-type

2ms

ETCTN 10500: Testing the Safety of the Anti-cancer Drugs Tazemetostat and Belinostat in Patients With Lymphomas That Have Resisted Treatment (clinicaltrials.gov)

P1, N=64, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

2 months ago

Trial suspension

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

RAS wild-type • EZH2 mutation • EZH2 wild-type

Tazverik (tazemetostat) • Beleodaq (belinostat)

2ms

Characterizing the Mutational Landscape of Diffuse Large B-Cell Lymphoma in a Prospective Cohort of Mexican Patients. (PubMed, Int J Mol Sci)

In conclusion, using a customized panel, we characterized the mutational landscape of a large cohort of Mexican DLBCL patients. These results need to be confirmed in further studies.

2 months ago

Journal

TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein)

TP53 mutation • EZH2 mutation

2ms

A new digital droplet PCR method for looking at epigenetics in diffuse large B-cell lymphomas: The role of BMI1, EZH2, and USP22 genes. (PubMed, Int J Lab Hematol)

High expression of BMI1 and of USP22 might be a poor prognostic factor in DLBCL, and might represent the target for novel inhibitors.

2 months ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • BMI1 (BMI1 proto-oncogene, polycomb ring finger) • GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase) • USP22 (Ubiquitin Specific Peptidase 22)

EZH2 mutation • BCL2 expression • BMI1 overexpression

6ms

EZH2 G553C significantly increases the risk of brain metastasis from lung cancer due to salt bridge instability. (PubMed, Cancer Cell Int)

EZH2 G553C polymorphism contributes to the prediction of brain metastasis of lung cancer, in which G allele carriers are more prone to brain metastasis.

6 months ago

Journal

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

EZH2 mutation

6ms

Evaluate the Safety and Clinical Activity of HH2853 (clinicaltrials.gov)

P1/2, N=254, Recruiting, Haihe Biopharma Co., Ltd. | N=168 --> 254

6 months ago

Enrollment change • Metastases

ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1)

ARID1A mutation • BAP1 mutation • EZH2 mutation • SMARCA4 mutation

HH2853

7ms

Single-Cell DNA Sequencing Reveals an Evolutionary Pattern of CHIP in Transplant Eligible Multiple Myeloma Patients. (PubMed, Cells)

Moreover, we observed a tendency of CHIP-positive patients to achieve a suboptimal response to therapy compared to those without. A sub-clone dynamic of high-fitness mutations over time was confirmed.

7 months ago

Journal

DNMT3A (DNA methyltransferase 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD34 (CD34 molecule)

DNMT3A mutation • ASXL1 mutation • TET2 mutation • EZH2 mutation

7ms

EZH2 mutations in follicular lymphoma distort H3K27me3 profiles and alter transcriptional responses to PRC2 inhibition. (PubMed, Nat Commun)

We also uncover unexpected variability in the mutational landscape of successive biopsies, pointing to frequent co-existence of different clones and cautioning against stratifying patients based on single sampling. Our results clarify how oncogenic PRC2 mutations disrupt chromatin and transcription, and the therapeutic vulnerabilities this creates.

7 months ago

Journal

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

EZH2 mutation • EZH2 Y641F • EZH2 Y641 • PRC2 mutation • EZH2 wild-type

7ms

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

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

7 months ago

Journal

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

TET2 mutation • EZH2 mutation • SRSF2 mutation

7ms

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.

7 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)

7ms

Discovery of novel pyridone-benzamide derivatives possessing a 1-methyl-2-benzimidazolinone moiety as potent EZH2 inhibitors for the treatment of B-cell lymphomas. (PubMed, Bioorg Med Chem)

In this study, based on the binding model of 1 (tazemetostat) with polycomb repressive complex 2 (PRC2), we designed and synthesized a series of tazemetostat analogs bearing a 1-methyl-2-benzimidazolinone moiety to improve the inhibitory activity of EZH2 wild-type (WT) and Y641 mutants and enhance metabolic stability...Additionally, N40 (T1/2 = 177.69 min) showed improved metabolic stability in human liver microsomes compared with 1 (T1/2 = 7.97 min). Our findings suggest N40 as a promising EZH2 inhibitor; further investigation remains warranted to confirm our findings and further develop N40.

7 months ago

Journal

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

EZH2 mutation • EZH2 Y641F • EZH2 Y641 • EZH2 wild-type

Tazverik (tazemetostat)

7ms

SYMPHONY-1: Study of Tazemetostat Versus Placebo When Given in Combination With Lenalidomide and Rituximab in Participants With Relapsed/Refractory Follicular Lymphoma (clinicaltrials.gov)

P3, N=612, Recruiting, Epizyme, Inc. | Trial completion date: Mar 2029 --> Apr 2032 | Trial primary completion date: Mar 2026 --> Sep 2029

7 months ago

Trial completion date • Trial primary completion date • Combination therapy

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

EZH2 mutation

Rituxan (rituximab) • lenalidomide • Tazverik (tazemetostat)

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

7 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)

7ms

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

7 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

8ms

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

8 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

8ms

Study of Valemetostat Tosylate as a Single Agent in Patients With Relapse/Refractory B-cell Lymphoma (clinicaltrials.gov)

P2, N=141, Active, not recruiting, The Lymphoma Academic Research Organisation | Recruiting --> Active, not recruiting | Trial completion date: Jun 2024 --> Oct 2024 | Trial primary completion date: Jun 2024 --> Oct 2024

8 months ago

Enrollment closed • Trial completion date • Trial primary completion date

SLC1A5 (Solute Carrier Family 1 Member 5)

EZH2 mutation

Ezharmia (valemetostat)

8ms

Evaluate the Safety and Clinical Activity of HH2853 (clinicaltrials.gov)

P1/2, N=168, Recruiting, Haihe Biopharma Co., Ltd. | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

8 months ago

Trial completion date • Trial primary completion date • Metastases

ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1)

ARID1A mutation • BAP1 mutation • EZH2 mutation • SMARCA4 mutation

HH2853

8ms

TP53 mutation is frequent in mantle cell lymphoma with EZH2 expression and have dismal outcome when both are present. (PubMed, Hum Pathol)

p53 mutant pattern is due to TP53 mutation. MCL patients with EZH2 expression or TP53 mutation show inferior outcome and when both are present, patients have dismal outcome.

8 months ago

Journal

TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)

TP53 mutation • EZH2 mutation • TP53 expression

8ms

P2, N=55, Not yet recruiting, Epizyme, Inc. | Initiation date: Dec 2023 --> Sep 2024

8 months ago

Trial initiation date

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

EZH2 mutation • EZH2 wild-type

Tazverik (tazemetostat)

8ms

ETCTN 10500: Testing the Safety of the Anti-cancer Drugs Tazemetostat and Belinostat in Patients With Lymphomas That Have Resisted Treatment (clinicaltrials.gov)

P1, N=64, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

8 months ago

Trial completion date • Trial primary completion date

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

RAS wild-type • EZH2 mutation • EZH2 wild-type

Tazverik (tazemetostat) • Beleodaq (belinostat)

9ms

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.

9 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

9ms

Clinical characteristics and prognosis of acute myeloid leukemia patients with Runt-related transcription factor 1 mutation: A single-center retrospective analysis. (PubMed, Hematol Oncol)

EZH2 co-mutation, DNMT3A co-mutation, old age and high WBC count were associated with inferior survival of AML-RUNX1mut . Allo-HSCT can significantly improve the prognosis of AML-RUNX1mut .

9 months ago

Retrospective data • Journal

NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • RAS (Rat Sarcoma Virus) • BCORL1 (BCL6 Corepressor Like 1)

NPM1 mutation • DNMT3A mutation • RUNX1 mutation • EZH2 mutation

9ms

Hypomethylating agents plus venetoclax compared with intensive induction chemotherapy regimens in molecularly defined secondary AML. (PubMed, Leukemia)

In pairwise comparisons adjusted for age, HMA + VEN was associated with improved OS vs. 7 + 3 in patients with SF3B1 mutation and improved OS vs. CPX-351 in those with RNA splicing factor mutations. In molecularly defined secondary AML treatment with HMA + VEN might be preferred but could further be guided by co-mutations.

9 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • SF3B1 (Splicing Factor 3b Subunit 1) • BCOR (BCL6 Corepressor)

KRAS mutation • NRAS mutation • SF3B1 mutation • EZH2 mutation

Venclexta (venetoclax) • Vyxeos (cytarabine/daunorubicin liposomal formulation)

10ms

A miniaturized mode-of-action profiling platform enables high throughput characterization of the molecular and cellular dynamics of EZH2 inhibition. (PubMed, Sci Rep)

The market approval of Tazemetostat (TAZVERIK) for the treatment of follicular lymphoma and epithelioid sarcoma has established "enhancer of zeste homolog 2" (EZH2) as therapeutic target in oncology...These inhibitors interact in a more entropy-driven fashion and show the most persistent effects in cellular washout and antiproliferative efficacy experiments. Our work provides mechanistic insights for the largest cohort of EZH2 inhibitors reported to date, demonstrating that-among several other binding parameters-target residence time is the best predictor of cellular efficacy.

10 months ago

Journal

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

EZH2 mutation • EZH2 Y641 • EZH2 wild-type

Tazverik (tazemetostat)

10ms

BMP-ACVR1 Axis is Critical for Efficacy of PRC2 Inhibitors in B-Cell Lymphoma. (PubMed, Adv Sci (Weinh))

Although PRC2 inhibitors, such as tazemetostat, have demonstrated anti-lymphoma activity in patients, the clinical efficacy is not limited to EZH2-mutant lymphoma...Furthermore, high levels of BMP6 and BMP7, along with ACVR1, are associated with longer survival in lymphoma patients, underscoring the clinical relevance of this study. Altogether, BMP-ACVR1 exhibits anti-lymphoma function and represents a critical PRC2-repressed pathway contributing to the efficacy of PRC2 inhibitors.

10 months ago

Journal

ACVR1 (Activin A Receptor Type 1) • BMP6 (Bone Morphogenetic Protein 6)

EZH2 mutation

Tazverik (tazemetostat)

10ms

Discovery of a germline EZH2 variant reveals Weaver syndrome during sequencing of a B-cell acute lymphoblastic leukemia (B-ALL) (ACMG 2024)

Hematologic malignancies developing in infancy and childhood - including ALL - have been described in two other patients with Weaver syndrome, although heightened cancer surveillance is not currently recommended. Interestingly, one of these patients - who harbored the same EZH2 E745K variant - developed non-Hodgkin lymphoma at 13 years old. This unusual case of ALL arising in both childhood and adulthood supports a potential link between Weaver syndrome and susceptibility to hematologic cancers.

10 months ago

TET2 (Tet Methylcytosine Dioxygenase 2)

EZH2 mutation

TruSight Myeloid Sequencing Panel

10ms

The Clinical Utility of Plasma Circulating Tumor DNA in the Diagnosis and Disease Surveillance in non-DLBCL non-Hodgkinâ€™s Lymphomas (ACMG 2024)

Plasma ctDNA demonstrated high concordance with tumor biopsy in detecting genetic aberrations for non-DLBCL NHLs and serves as a promising surrogate of tumor biopsy in monitoring treatment response and disease progression in non-DLBCL NHLs.

10 months ago

Clinical • Tumor mutational burden • IO biomarker • Circulating tumor DNA

TMB (Tumor Mutational Burden) • BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1)

EZH2 mutation

Hemasalus™

10ms

FLT3 tyrosine kinase inhibition modulates PRC2 and promotes differentiation in acute myeloid leukemia. (PubMed, Leukemia)

These results demonstrate that in addition to its known cell survival and proliferation signaling, FLT3-ITD has a second, previously undefined function to maintain a myeloid stem/progenitor cell state through modulation of PRC2 activity. Our findings support exploring EZH1/2 inhibitors as therapy for FLT3-ITD AML.

10 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

FLT3-ITD mutation • EZH2 mutation

11ms

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

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

11 months ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • STAG2 (Stromal Antigen 2) • SETBP1 (SET Binding Protein 1)

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

11ms

NUP214 Rearrangements in Leukemia Patients: A Case Series From a Single Institution. (PubMed, Ann Lab Med)

We examined the characteristics and concurrent test results, including gene mutations, of 11 leukemia patients with NUP214 rearrangement. We hope that the elucidation of the context in which they occurred will aid future research on tailored monitoring and treatment.

11 months ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NOTCH1 (Notch 1) • WT1 (WT1 Transcription Factor) • NUP214 (Nucleoporin 214)

EZH2 mutation

11ms

Performance of the cobas EZH2 mutation test on clinical samples from non-Hodgkin lymphoma patients. (PubMed, PLoS One)

cobas EZH2 Test data demonstrated that the test is reliable and will perform well in a commercial customer environment.

11 months ago

Journal

EZH2 mutation

cobas® EZH2 Mutation Test

11ms

Epigenetic vulnerabilities of leukemia harboring inactivating EZH2 mutations. (PubMed, Exp Hematol)

The identified EZH2 mutations had drastically reduced catalytic activity, resulting in lower cellular H3K27me3 levels and were associated with decreased EZH2 and PRC2 component EED protein levels. Overall, this study provides an important understanding of the role of EZH2 dysregulation in blood cancers and may indicate disease etiology for these poor prognosis AML and MDS/MPN cases.

11 months ago

Journal

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

EZH2 mutation

11ms

Recurrent mutations in Refractory/Relapsed Diffuse Large B cell Lymphoma by targeted gene sequencing. (PubMed, Cytogenet Genome Res)

Co-occurrence of loss of function mutations of TNFAIP3 and missense mutations in MYD88 was associated with a non-responsive cohort. Discussion-The study highlights mutations associated with chemotherapeutic response in DLBCL with implications for initial diagnostic biopsy response prediction.

11 months ago

Journal

TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • TNFAIP3 (TNF Alpha Induced Protein 3) • CD58 (CD58 Molecule)

TP53 mutation • NOTCH1 mutation • MYD88 mutation • EZH2 mutation

12ms

A Novel and Potent EZH1/2 Dual Inhibitor, HM97662 Demonstrated a Wide Spectrum of Therapeutic Potential for Hematological Malignancies (ASH 2023)

The enhancer of zeste homolog 2 (EZH2) and its homolog EZH1 are catalytic components of polycomb repressive complex 2 (PRC2), which tri-methylate histone H3 at lysine 27 (H3K27me3) to repress transcription of their target genes. In conclusion, the present preclinical studies demonstrated that HM97662, an EZH1/2 dual inhibitor, had a promising and wide spectrum of therapeutic potential for hematological malignancies. It is urgent to assess the effectiveness of HM97662 in further clinical trials.

12 months ago

IO biomarker

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • CD38 (CD38 Molecule) • PRDM1 (PR/SET Domain 1) • CDKN1C (Cyclin Dependent Kinase Inhibitor 1C) • SUZ12 (SUZ12 Polycomb Repressive Complex 2 Subunit)

EZH2 mutation • EZH2 Y641 • EZH2 overexpression

27 • HM97662