News - EZH2 mutation - LARVOL VERI

Posterior fossa ependymoma harboring H3K27M mutation: A rare case report with clinical follow-up and diagnostic challenges. (PubMed, Clin Neuropathol)

While H3K27M mutations are hallmark features of diffuse midline gliomas, rare cases of posterior fossa ependymomas harboring these mutations have been reported. Recent studies suggest molecular similarities between diffuse midline gliomas and posterior fossa ependymomas expressing H3K27M and EZHIP, potentially reflecting shared hindbrain developmental programs in their biological origins.

3 days ago

Journal

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • GFAP (Glial Fibrillary Acidic Protein) • OLIG2 (Oligodendrocyte Transcription Factor 2)

EZH2 mutation

MDS/AML and AML with myelodysplasia-related gene mutations: clinical and molecular similarities. (PubMed, Blood Adv)

MRD of secondary type mutations alone lacks predictive value, yet MRD of non-DTA mutations in CR is associated with increased CIR in st-AML (SHR MRDpos vs. MRDneg 3.25; p<0.001). Molecularly-defined st-AML, including st-MDS/AML, defines a distinct AML category with a unique genetic, clinical and treatment response profile, in which NGS-based MRD holds markedly prognostic significance.

9 days ago

Journal

SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • ETV6 (ETS Variant Transcription Factor 6) • 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)

ASXL1 mutation • SF3B1 mutation • EZH2 mutation • SRSF2 mutation

13d

To Evaluate a Phase I/II Clinical Study of XNW5004 Tablets in Patients With Relapsed/Refractory Advanced Tumors (clinicaltrials.gov)

P1/2, N=120, Completed, Evopoint Biosciences Inc. | Recruiting --> Completed | N=176 --> 120 | Trial completion date: Dec 2024 --> Aug 2025 | Trial primary completion date: Dec 2024 --> Aug 2025

13 days ago

Trial completion • Enrollment change • Trial completion date • Trial primary completion date

TNFRSF8 (TNF Receptor Superfamily Member 8)

EZH2 mutation

XNW5004

16d

Phosphorylation-dependent modulation of the Lamin A/C-EZH2 complex regulates epithelial-mesenchymal plasticity. (PubMed, Nucleic Acids Res)

In vivo, xenograft assays in NOD-SCID mice reveal that while phosphorylated Lamin A/C or EZH2 promote tumor growth and metastasis, phospho-deficient mutants markedly suppress it. Lamin A/C-EZH2 interaction regulates the expression of E-M-associated transcription factors, highlighting the role of this interaction in modulating transcriptional plasticity, thereby serving as a potential therapeutic target for regulating metastasis in breast cancers.

16 days ago

Journal

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • LMNA (Lamin A/C) • TWIST1 (Twist Family BHLH Transcription Factor 1) • CDK1 (Cyclin-dependent kinase 1) • SNAI1 (Snail Family Transcriptional Repressor 1) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)

EZH2 mutation

20d

A Study of Tazemetostat on Safety in Participants With Relapsed or Refractory Follicular Lymphoma With Enhancer of Zeste Homolog 2 (EZH2) Gene Mutation in Japan (clinicaltrials.gov)

P=N/A, N=145, Active, not recruiting, Eisai Co., Ltd. | Recruiting --> Active, not recruiting

20 days ago

Enrollment closed

EZH2 mutation

Tazverik (tazemetostat)

22d

Correlation of EZH2 and related signaling molecules p-STAT3, p-ERK1/2, and MYC overexpression with H3K27 trimethylation associates differently to disease progression in JAK2 mutation -positive and -negative myeloid neoplasms. (PubMed, Leuk Lymphoma)

EZH2, p-STAT3, MYC, and p-ERK1/2 upregulation associate differently with disease progression depending on JAK2 mutation status. EZH2 and related signaling molecules could serve as potential therapeutic targets in myeloid neoplasms.

22 days ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • JAK2 (Janus kinase 2) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • STAT3 (Signal Transducer And Activator Of Transcription 3)

EZH2 mutation

29d

Polycomb Repressive Complexes as Therapeutic Targets in Hematologic Malignancies. (PubMed, Exp Hematol)

Therapeutic targeting of H3K27me3 with EZH2-selective inhibitors such as tazemetostat has shown clinical benefit in lymphoma; however, their efficacy is limited by functional redundancy with EZH1. The dual EZH1/2 inhibitor valemetostat overcomes this limitation by reactivating tumor suppressor genes, achieving durable responses in ATL and peripheral T-cell lymphoma (PTCL). Nonetheless, therapeutic resistance can emerge through PRC2 gatekeeper mutations and compensatory DNA methylation. These findings underscore the value of targeting the dysregulated epigenome and support the continued clinical development of dual EZH1/2 inhibitors.

29 days ago

Review • Journal

EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein) • BCOR (BCL6 Corepressor) • BMI1 (BMI1 proto-oncogene, polycomb ring finger) • SUZ12 (SUZ12 Polycomb Repressive Complex 2 Subunit)

EZH2 mutation

Tazverik (tazemetostat) • Ezharmia (valemetostat)

CSF3R Mutations Imply Adverse Prognostic Impact in Adult Acute Myeloid Leukemia Patients: A Single-Center Retrospective Study. (PubMed, Cancer Med)

CSF3R mutations define a distinct, high-risk AML subset characterized by an inferior treatment response and survival, warranting incorporation into future risk stratification.

1 month ago

Retrospective data • Journal

NPM1 (Nucleophosmin 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • CSF3R (Colony Stimulating Factor 3 Receptor) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

NPM1 mutation • ASXL1 mutation • EZH2 mutation • SRSF2 mutation

ALLO-BAT: Study of Stem Cell Transplant vs. Non-Transplant Therapies in High-Risk Myelofibrosis (clinicaltrials.gov)

P=N/A, N=90, Recruiting, University Health Network, Toronto | Trial completion date: Feb 2026 --> Dec 2026 | Trial primary completion date: Aug 2025 --> Dec 2026

1 month ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • 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) • CALR (Calreticulin)

TP53 mutation • ASXL1 mutation • EZH2 mutation • SRSF2 mutation • CALR mutation

Jakafi (ruxolitinib) • hydroxyurea

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: Jun 2026 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

1 month 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 • SRSF2 mutation • Chr del(5q)

cytarabine • Pemazyre (pemigatinib) • daunorubicin • Starasid (cytarabine ocfosfate)

Loss of Ezh2 precipitates lethal disease progression in a mouse model of Calr-mutated myeloproliferative neoplasms. (PubMed, Exp Hematol)

To investigate this question, we used a knock-in mouse that constitutively expresses a Calr frameshift allele and introduced conditional Ezh2 deletion triggered by tamoxifen...Short-term colony assays showed that inhibition of PPARγ modestly increased the anti-proliferative effect of cytarabine on AML-derived stem and progenitor cells, suggesting a possible reliance on FAO...At a non-critical stage, peripheral counts remain near-normal while bone marrow HSPC compartments are already distorted. AML-like, but not sMF-like, Flk2- CD48+ LSK cells transmit leukemia and display enhanced fatty-acid-oxidation signatures, suggesting a distinct, potentially targetable metabolic bias.

1 month ago

Preclinical • Journal

FLT3 (Fms-related tyrosine kinase 3) • CALR (Calreticulin) • PPARG (Peroxisome Proliferator Activated Receptor Gamma) • CD48 (CD48 Molecule)

EZH2 mutation • CALR mutation

tamoxifen • cytarabine

Atypical chronic myeloid leukemia: From diagnosis to molecular features and therapeutic options. (PubMed, Hemasphere)

The most used agents include hydroxyurea, interferon, hypomethylating agents, and JAK inhibitors, although none of them are disease-modifying. Allogeneic hematopoietic stem cell transplant remains the only potentially curative approach and should be considered in all eligible patients. Actionable mutations (CSF3R, NRAS/KRAS, and KIT) have also been identified, supporting the development of new agents targeting the involved pathways.

1 month ago

Review • Journal

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CSF3R (Colony Stimulating Factor 3 Receptor) • SETBP1 (SET Binding Protein 1) • ETNK1 (Ethanolamine Kinase 1)

KRAS mutation • NRAS mutation • KIT mutation • ASXL1 mutation • TET2 mutation • EZH2 mutation • CBL mutation • SRSF2 mutation

hydroxyurea