Lymphoid Neoplasm

All lines of conventional therapy (including allogeneic HSCT, blinatumomab, and CAR T cells) were inefficient for a 6-year-old boy with B-cell ALL and CNS infiltration (National Cancer Institute high … (full text at CIViC)

PMID 31725893 · Schewe et al., 2019 · Open in CIViC

ETV6-RUNX1 rearranged leukemia is a well established diagnostic entity in the WHO classification of leukemia. It is designated as B-lymphoblastic leukemia/lymphoma with t(12;21)(p13.2;q22.1); ETV6-RUN… (full text at CIViC)

PMID 27069254 · Arber et al., 2016 · Open in CIViC

In this study, the authors investigated the role of the ETV6::RUNX1 fusion in the diagnosis of B-lymphoblastic leukemia/lymphoma. B-ALL is a heterogeneous disease, and identifying cytogenetic abnormal… (full text at CIViC)

PMID 9226156 · Borkhardt et al., 1997 · Open in CIViC

Somewhat rare but recurrent mutations have been described

PMID 32160292 · Pararajalingam et al., 2020 · Open in CIViC

In this 2013 study, the authors analyzed 366 follicular lymphoma (FL) patients with additional paired samples from 33 cases of transformed FL. Patients harbored EZH2 mutations predominantly at codons … (full text at CIViC)

PMID 24052547 · Bödör et al., 2013 · Open in CIViC

In this 2020 study, the authors analyzed four cases of follicular lymphoma using circulating tumor DNA and droplet digital PCR to monitor EZH2 hotspot mutations, including A682G. One patient with tran… (full text at CIViC)

PMID 32668764 · Nagy et al., 2020 · Open in CIViC

In this 2011 study, the authors analyzed tumor and matched normal DNA and RNA from 127 cases of B-cell non-Hodgkin lymphoma to identify recurrent somatic variants. EZH2 A682G and A638G were identified… (full text at CIViC)

PMID 21796119 · Morin et al., 2011 · Open in CIViC

In this study, 366 patients with follicular lymphoma were analyzed using next-generation sequencing and Sanger sequencing to evaluate EZH2 variants. EZH2 variants were identified in 101 patients (27.6… (full text at CIViC)

PMID 24052547 · Bödör et al., 2013 · Open in CIViC

In this study, tumor and matched normal DNA and RNA from 127 cases of B-cell non-Hodgkin lymphoma were analyzed to identify recurrent somatic variants. EZH2 A692V was identified in one lymphoma case. … (full text at CIViC)

PMID 21796119 · Morin et al., 2011 · Open in CIViC

Tazemetostat was found to have increased anti-tumor activity in patients with relapsed/refractory follicular lymphoma with gain-of-function EZH2 mutations (cobas EZH2 Mutation Test; objective response… (full text at CIViC)

PMID 33035457 · Morschhauser et al., 2020 · Open in CIViC

In this phase I study, four Japanese patients with follicular lymphoma were recruited to test the efficacy of EZH2 inhibitor-Tazemetostat. Patients were screened for presence of EZH2 mutations and onl… (full text at CIViC)

PMID 33492746 · Munakata et al., 2021 · Open in CIViC

In this phase I study (clinical trial NCT03009344), one patient with germinal center B‐cell‐like (GCB) DLBCL and two with non-GCB DLBCL types were recruited to test the efficacy of EZH2 inhibitor-Taze… (full text at CIViC)

PMID 33492746 · Munakata et al., 2021 · Open in CIViC

In advanced stage follicular lymphoma patients receiving rituximab + chemotherapy (R-CHOP or R-CVP), EZH2 mutations were associated with better failure free survival in patients with high-risk FLIPI s… (full text at CIViC)

PMID 26256760 · Pastore et al., 2015 · Open in CIViC

Heterozygous mutations in EZH2 at Y641 were the second most frequent genetic event (after BCL2 t(14;18)) associated with a diagnosis of GCB-DLBCL in 35 / 320 patient samples. In contrast, mutations in… (full text at CIViC)

PMID 20081860 · Morin et al., 2010 · Open in CIViC

Heterozygous mutations in EZH2 at Y641 were the second most frequent genetic event (after BCL2 t(14;18)) associated with a diagnosis of Follicular non-Hodgkin Lymphoma in 18 / 251 patient samples. In … (full text at CIViC)

PMID 20081860 · Morin et al., 2010 · Open in CIViC

A selective EZH2 inhibitor (EI1) and siRNA were used to inhibit EZH2 Y641F mutation in DLBCL mutated cell line (WSU-DLCL2). Two independent siRNAs knocked down EZH2 mRNA by almost 80% and inhibited c… (full text at CIViC)

PMID 23236167 · Qi et al., 2012 · Open in CIViC

In this preclinical study, authors aimed to study EZH2 inhibition effect on PRAME in DLBCL. IμBcl6 EZH2-Y646F Cγ1-Cre mice were used for in vivo experiment using a vehicle or EZH2 inhibitor, EPZ011989… (full text at CIViC)

PMID 35380993 · Takata et al., 2022 · Open in CIViC

A phase I safety and dose-escalation study (NCT01897571) was completed for tazemetostat in relapsed or refractory B-cell non-Hodgkin lymphoma or advanced solid tumors. Durable objective responses, inc… (full text at CIViC)

PMID 29650362 · Italiano et al., 2018 · Open in CIViC

A selective EZH2 inhibitor (EI1) was used to target the EZH2 Y641N mutation in DLBCL cell lines. EI1 treatment significantly inhibited proliferation in EZH2-mutated cells compared to lymphoma cells wi… (full text at CIViC)

PMID 23236167 · Qi et al., 2012 · Open in CIViC

EZH2 inhibitor, GSK126, showed high potency against DLBCL cell line, KARPAS-422, which harbors the variant Y646N, and resulted in cellular proliferation inhibition after six days (growth IC50 = 232 n… (full text at CIViC)

PMID 23051747 · McCabe et al., 2012 · Open in CIViC

In this large cohort study, 366 patients with follicular lymphoma (FL) were recruited to investigate the incidence and distribution of EZH2 mutations. NGS and Sanger detected EZH2 positive mutations i… (full text at CIViC)

PMID 24052547 · Bödör et al., 2013 · Open in CIViC

In a multicentre, open-label, phase 1 trial, tazemetostat was evaluated in 64 adult patients (≥18 years) with relapsed or refractory B-cell non-Hodgkin lymphoma (n=21) or advanced solid tumours (n=43)… (full text at CIViC)

PMID 29650362 · Italiano et al., 2018 · Open in CIViC

This study used a combination of RNA-seq, whole genome and targeted sequencing to identify recurrently mutated genes in follicular and diffuse large B-cell lymphoma. They reported 30 genes that had si… (full text at CIViC)

PMID 21796119 · Morin et al., 2011 · Open in CIViC

Described in multiple studies

PMID 30617194 · Grande et al., 2019 · Open in CIViC

In mouse models, constitutive NOTCH signaling contributes to the genesis of breast cancer, medulloblastoma, and T cell leukemia, whereas in human cancer its role is best exemplified by T cell acute ly… (full text at CIViC)

PMID 17646409 · O'Neil et al., 2007 · Open in CIViC

Cell line LP1 expressing FGFR3 F384L was treated with small molecule inhibitor PKC412, with relative viability rising above 1.1/1.0 at both 50 nM and 100 nM. Relative viability dropped to 0.96/1.0 at … (full text at CIViC)

PMID 16091734 · Chen et al., 2005 · Open in CIViC

Analysis of a single patient is reported from a phase II trial (NCT02952573) testing erdafitinib in relapsed/refractory myeloma patients with or without FGFR3 mutations. The single patient (52 year ol… (full text at CIViC)

PMID 36639200 · Croucher et al., 2023 · Open in CIViC

The study found that FGFR3 interacts with a regulatory subunit of PI3K, and this interaction negatively regulates the Ras/ERK/MAPK pathway in response to FGFR3 activity. This interaction could be a po… (full text at CIViC)

PMID 19286672 · Salazar et al., 2009 · Open in CIViC

Xenografts of multiple myeloma cell line OPM2 (FGFR3 K650E) into nude mice resulted in tumor growth.

PMID 19381019 · Qing et al., 2009 · Open in CIViC

PKC412 inhibited the growth of FGFR3 K650E-transformed Ba/F3 cells. Researchers introduced an N540D mutation to FGFR3-transformed Ba/F3 cells, which reduces inhibition of the FGFR3 K650E-transformed c… (full text at CIViC)

PMID 16091734 · Chen et al., 2005 · Open in CIViC

In culture, monoclonal antibody R3Mab treatment inhibited the growth of multiple myeloma cell line UTMC-2 which has wild type FGFR3 but did not affect proliferation of multiple myeloma cell line KMS11…

Ba/F3 cells transformed with FGFR3 K650E or TEL-FGFR3 had mutation FGFR3 N540D introduced to determine whether the FGFR3 mutants were the critical targets for PKC412-mediated cytotoxicity. The cells t… (full text at CIViC)

PMID 16091734 · Chen et al., 2005 · Open in CIViC

Multiple myeloma (MM) is a neoplastic disorder of clonal B cells characterised by uncontrolled and aberrant proliferation of plasma cells within bone marrow, monoclonal protein in the blood or urine, … (full text at CIViC)

PMID 25402977 · Scheid et al., 2015 · Open in CIViC

Pro-B Ba/F3 cells transfected with wild type FGFR3 resulted in Il-3 independence with FGF1 dependence for growth. Monoclonal antibody R3Mab treatment in addition to FGF1 resulted in suppression of pro… (full text at CIViC)

PMID 19381019 · Qing et al., 2009 · Open in CIViC

Ba/F3 cells transfected with wild type FGFR3 or common bladder carcinoma variant FGFR3 Y375C both resulted in IL-3 independence with FGF1 dependence for growth. However, tumors grew when multiple myel… (full text at CIViC)

PMID 19381019 · Qing et al., 2009 · Open in CIViC

t(4;14) positive multiple myeloma cell line OPM-1 and KMS11 expressing FGFR3 Y373C were inhibited by PKC412, with relative viability dropping to 0.9/1.0 at 100 nM, 0.8/1.0 to 200 nM, 0.58/1.0 at 400 … (full text at CIViC)

PMID 16091734 · Chen et al., 2005 · Open in CIViC