EVI1 Blocking Peptide
- Known as:
- EVI1 Blocking Peptide
- Catalog number:
- 33r-9619
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Fitzgerald industries international
- Gene target:
- EVI1 Blocking Peptide
Related genes to: EVI1 Blocking Peptide
- Gene:
- MECOM NIH gene
- Name:
- MDS1 and EVI1 complex locus
- Previous symbol:
- MDS1, EVI1
- Synonyms:
- MDS1-EVI1, PRDM3, KMT8E
- Chromosome:
- 3q26.2
- Locus Type:
- gene with protein product
- Date approved:
- 1990-07-10
- Date modifiied:
- 2019-04-23
Related products to: EVI1 Blocking Peptide
Related articles to: EVI1 Blocking Peptide
- Acute myeloid leukaemia (AML) with MDS1 and EVI1 complex locus (MECOM) rearrangement is recognized by the World Health Organization as a distinct entity characterized by poor prognosis and aggressive disease progression. This rearrangement evokes aberrant ecotropic viral integration site 1 (EVI1) overexpression, which enhances leukaemic stem cell self-renewal and drives chemoresistance. However, the mechanisms by which EVI1 contributes to venetoclax resistance remain unclear. In this study, patients with AML were stratified into the EVI1-high and EVI1-low groups based on transcript levels. The EVI1-high subgroup exhibited significantly inferior clinical outcomes and reduced complete remission rates following chemotherapy or venetoclax-based regimens. Meanwhile, we demonstrated that elevated EVI1 expression confers resistance to venetoclax by stabilizing myeloid cell leukaemia 1 (MCL-1) through activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway in vitro. Mechanistically, elevated EVI1 levels were associated with increased phosphorylation of MCL-1 at threonine 163 (T163pMCL-1), thereby stabilizing MCL-1 by attenuating its ubiquitin-proteasome-mediated degradation. Importantly, cotreatment with venetoclax and the clinically available AKT inhibitor capivasertib effectively restored sensitivity in both cell lines and patient-derived primary AML samples with high EVI1 expression. Overall, our findings reveal a novel molecular mechanism underlying EVI1-mediated venetoclax resistance through PI3K/AKT-driven MCL-1 stabilization and suggest a combination strategy involving AKT inhibition as a promising approach for overcoming therapeutic resistance in this high-risk AML subset. - Source: PubMed
Publication date: 2026/06/04
Zhou JiayinKui XiangjieHuang DanZhang XuehongHao YuchaoXie FangLou JiachengYan Jinsong - We summarize the technical principles of optical genome mapping (OGM) and evaluate its current clinical applications across myeloid neoplasms, with emphasis on acute myeloid leukemia and myelodysplastic syndromes. We highlight evidence demonstrating high concordance with standard cytogenetic methods, while also showing incremental diagnostic yield through detection of cryptic abnormalities and/or refinement complex rearrangements. We further discuss clinically relevant cytogenomic abnormalities that may be underrecognized by conventional cytogenetics, including chromoanagenesis, KMT2A partial tandem duplication and cryptic rearrangements involving genes such as NUP98 and MECOM. We also address practical considerations for implementation of OGM in a clinical cytogenetic laboratory, including pre-analytical DNA quality requirements, assay sensitivity, bioinformatic interpretation and workflow integration. Current data support OGM as a complementary component of genomic workups rather than a replacement for all existing assays. As analytical standards mature and outcome-linked evidence expands, OGM has strong potential to improve genomic risk stratification, refine disease classification and advance precision diagnostics in myeloid neoplasms. - Source: PubMed
Publication date: 2026/05/30
Tang GuilinWei QingKlausner MelanieZou Ying SToruner Gokce A - Glioblastoma (GBM) exhibits metabolic plasticity, relying on mitochondrial oxidative phosphorylation (OXPHOS) to support migration and therapy resistance. Although mitochondrial calcium overload typically induces apoptosis, GBM cells maintain viability under high calcium conditions. The structural and metabolic coupling mechanisms underlying this adaptation remain incompletely understood. Here, we identify a mitochondria-associated membranes (MAMs) regulatory axis driven by a positive feedback loop between the mitochondrial calcium uniporter (MCU) and the transcription factor MECOM. Using multi-omics profiling, time-resolved functional assays, and mitochondrial transfer experiments, we show that MCU-mediated calcium influx expands MAMs without triggering cell death. This influx initiates adaptive mitochondrial cristae remodeling via the Mic10/Mic60 complex and activates selective mitophagy. Pharmacological blockade and autophagy-rescue experiments (using si-ATG5 and chloroquine) indicate that this mitophagy-dependent quality control promotes tumor migration and buffers reactive oxygen species (ROS) to sustain OXPHOS capacity. Targeting the MCU-MECOM axis induces metabolic suppression and reduces glioma cell viability. To translate these findings into a diagnostic application, we developed MAMs-Net, a deep-learning framework for the automated quantification of MAMs ultrastructure from transmission electron microscope (TEM) images. In an independent external validation cohort, MAMs-Net achieved an AUC of 0.95 for glioma pathological stratification. This study characterizes an MCU-MECOM structural-metabolic circuit that supports GBM survival under calcium overload, identifying a potential therapeutic target and providing a pathophysiologically interpretable, AI-driven tool for glioma evaluation. - Source: PubMed
Publication date: 2026/05/01
Li XiaodongWang YaoliangWu FeifeiHuang XinNi ZiweiXu GuangzhenWang WeizhongTie JingjingHuang YunqiangSun YuzeWang ZhenhuaLi ShujiaoZheng QianwenLiu YuxuanWu YoushengGong ChengrongGuo QingdongYang YanlingWang Yayun - X-linked lymphoproliferative syndrome type 1 (XLP1) is an inborn error of immunity caused by pathogenic variants in and is frequently complicated by Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs). However, cases of LPD without EBV infection have been reported and remain poorly understood. We investigated tumorigenesis mechanisms through transcriptomic profiling and somatic variant analysis in tumor samples from six patients with XLP1. Pathogenic variants were identified in two: one developed two distinct LPDs harboring / and variants, while the other carried , , , and variants. Transcriptome analysis of three tumors, compared with diffuse large B cell lymphoma from patients without an underlying immune defect, revealed a distinct expression profile. Gene Ontology analysis showed upregulation of adaptive immune response genes, including various and genes, suggesting polyclonal lymphocyte proliferation. Overall, LPD associated with XLP1 may originate from polyclonal lymphocyte expansion, either in the presence or absence of EBV infection, and subsequently progress to malignancy through somatic variants. - Source: PubMed
Publication date: 2026/03/12
Tomomasa DanNishimura AkiraYoshida KenichiNamikawa YuiKim Doo RiSakata NaokiSakamoto KenichiTaga TakashiSakai YutaIkawa YasuhiroIshida ToshiakiShin AreumYoo Keon HeeKim Yae-JeanOgawa SeishiHoshino AkihiroMorio TomohiroTakagi MasatoshiKanegane Hirokazu - Hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT) have a poor prognosis and are underrepresented in global clinical trials. We conducted a single-arm phase 2 study (DurHope) enrolling 30 patients with Vp3/4 PVTT receiving durvalumab plus hepatic arterial infusion therapy (HAIC) of FOLFOX regimen (fluorouracil, leucovorin, and oxaliplatin) as first-line treatment. Primary endpoint was 1-year overall survival (OS) rate, and secondary endpoints included progression-free survival, objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, and safety. The pre-specified study endpoints were achieved, the 1-year OS rate was 63.3%, with a median OS of 13.9 months (95% CI, 10.7-not reached [NR]) at the final analysis. In exploratory, post hoc biomolecular analyses, tumor single-nucleus RNA sequencing revealed chemotherapy resistance and immune escape signatures in nonresponders, including a MECOM+ malignant subcluster. Responders showed increased immune infiltration and stronger immune-tumor interactions. Peripheral blood dynamic single-cell RNA sequencing demonstrated expanded T-cell subsets and increased expression of cytotoxic-related genes after treatment, which was more pronounced in responders. This was accompanied by decreased nonclassical monocyte frequency and attenuated anti-inflammatory phenotype in responders. Findings were validated by immunohistochemistry and in vivo models. These data suggested the promising efficacy and generally tolerable toxicity of Durvalumab plus HAIC-FOLFOX in patients with Vp4 PVTT and provided candidate biomarkers. ClinicalTrials.gov number: NCT04945720. - Source: PubMed
Publication date: 2026/05/18
Yi JunzheWang JiongliangZhang YiminJiang XiongyingChen SongXu JieWu XintongZhong SuixingChen QifengHu YueSong YujiaTan GenjunZhang YunanLi JibinZhao MingLyu Ning