Ask about this productRelated genes to: PLCG2 antibody
- Gene:
- PLCG2 NIH gene
- Name:
- phospholipase C gamma 2
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 16q24.1
- Locus Type:
- gene with protein product
- Date approved:
- 1994-05-16
- Date modifiied:
- 2019-04-23
Related products to: PLCG2 antibody
Related articles to: PLCG2 antibody
- Bruton tyrosine kinase inhibitors (BTKi) are successful in treatment of chronic lymphocytic leukemia (CLL), yet acquired resistance remains a challenge. In our study, REC-1 cells that acquired resistance to BTKi tirabrutinib by long-term treatment gained a splice-site mutation (SSM) c.2236-1G>T in PLCG2. Notably, a deletion spanning c.2236-23_2238 at the same splice site (SSD) was identified in CLL from a patient who had disease progression during ibrutinib therapy. These alterations resulted in the exon-skipped variant, ∆21, which exhibited enhanced phospholipase activity. PLCG2 SSM REC-1 exhibited increased anti-IgM-mediated calcium flux and resistance to BTK inhibition but retained sensitivity to PLCγ inhibitors. By analyzing additional primary CLL samples, we identified widespread expression of two additional exon-skipped variants, ∆22 and ∆20-22, independent of PLCG2 genetic alterations. The active ∆20-22, which is also described in PLCG2-associated immune dysregulation (PLAID), was predominantly present in CLL compared to healthy donor samples. Expression analysis in CLL cells isolated from patients before and after targeted treatments revealed a decrease in expression of ∆20-22 post-venetoclax (p = 0.02)while no change in expression was observed after ibrutinib treatment, indicating that these variants may persist in the presence of ibrutinib but might be lost in the absence of drug selection pressure. Our study reveals novel PLCG2 splice-site alterations and exon-skipped variants beyond the classical BTK or PLCG2 mutations, to have a potential role in BTKi resistance and inform treatment selection. - Source: PubMed
Publication date: 2026/06/05
Qi JialeiLi WenDheenadayalan Rashmi PriyadharshiniYosifov Deyan YordanovDrewes CosimaWist MartinWieczorek MarcelSchmid VeraHobeika EliasGao XiangEndres SaschaSchneider ChristofRiecke ArminBarth HolgerGierschik PeterSiebert ReinerTausch EugenStilgenbauer StephanJebaraj Billy Michael Chelliah - Resistance to Bruton tyrosine kinase (BTK) inhibitors remains a major clinical challenge in B-cell lymphomas and often occurs in the absence of BTK or PLCG2 mutations. Here, we investigated non-genetic mechanisms of ibrutinib resistance in marginal zone lymphoma (MZL) and their broader therapeutic implications. Chronic ibrutinib exposure generated a resistant MZL model that showed cross-resistance to BTK inhibitors and degraders, without evidence of multidrug resistance or genetic alterations. Integrated transcriptomic, epigenetic, and proteomic analyses revealed extensive reprogramming, including activation of PI3K/AKT, MAPK, and MYC pathways, repression of apoptosis and oxidative phosphorylation, and a prominent cytokine-secretory phenotype. Interleukin-16 (IL-16) emerged as a central mediator of resistance. IL-16 was transcriptionally upregulated, actively secreted, and sufficient to induce ibrutinib resistance across multiple CD9-positive models of MZL, mantle cell lymphoma, chronic lymphocytic leukemia (CLL), and activated B-cell-like diffuse large B-cell lymphoma. Serum IL-16 levels were elevated in ibrutinib-refractory CLL patients without BTK/PLCG2 mutations. Mechanistically, IL-16 engaged CD9-enriched membrane microdomains to activate PI3Kδ, thereby sustaining AKT and ERK signaling, stabilizing MYC, inducing NF-κB-dependent programs, and upregulating antiapoptotic effectors, including BFL1 (BCL2A1). Pharmacological or genetic disruption of the IL-16/CD9/PI3K axis restored sensitivity to BTK inhibitors and R-CHOP and abrogated IL-16-induced signaling in primary CLL samples. In conclusion, an IL-16/CD9-driven, epigenetically regulated survival pathway represents one possible mechanism of resistance to BTK inhibitors and chemoimmunotherapy, supporting therapeutic targeting of this axis in refractory B-cell lymphomas. - Source: PubMed
Publication date: 2026/05/29
Arribas Alberto JCannas EleonoraSartori GiulioGuidetti FrancescaCascione LucianoNapoli SaraForestieri GabrielaFuzio FedericaPesenti Emma Daniela SusannaTarantelli ChiaraSpriano FilippoZucchetto AntonellaRossi Francesca MariaBruscaggin AlessioRinaldi AndreaCastro de Moura ManuelJovic SandraRaimondi AndreaBordone Pittau RobertaTerzi di Bergamo LodovicoYe XiaofeiStathis AnastasiosBen-David YaacovPan-Hammarström QiangSimonetta FedericoStussi GeorgZucca EmanueleGattei ValterBrown Jennifer REsteller ManelRossi DavideBertoni Francesco - Little is known about the long-term prognosis of patients with talaromycosis and inborn errors of immunity (IEI). - Source: PubMed
Publication date: 2026/05/13
Lu QianLi XianghuiJiang ZhiwenLi TiantianLi BingkunHuang LanHuang QihuaHu DongmeiLv ChunyingLiu GuoqunZhong JialingLin JingjingLiao LiuweiQin QianfengQin ShaShao HaotianWang ZhiyiLi XiuyingJiang LiZhang XinyuWei LiliLiang JiarongZheng DongyanWang ShuangjieWu WeixuanPan KaisuZheng YanqingLi YanningTang QingJiang MinLiao WanqingCao Cunwei - B cells are integral components of the tumor microenvironment (TME) and influence the progression, prognosis, and immunotherapy response of gastric cancer (GC). However, the prognostic relevance of germline variants in B cell-related immune genes remains undefined. We performed a two-stage genome-wide association analysis to identify single-nucleotide polymorphisms (SNPs) in B cell-related immune genes associated with overall survival (OS) in patients with pathologic tumor-node-metastasis (pTNM) stage I-III GC. Clinical, follow-up, and genome-wide association study (GWAS) genotyping data were analyzed from two independent Eastern Chinese cohorts (Shanghai, N = 2211; Jiangsu, N = 1049). Functional annotation, quantitative trait loci (QTL), and immune infiltration analyses were conducted. Among 15,857 SNPs across 223 genes, 210 were associated with OS in the discovery cohort, nine of which were validated. Two independent functional variants-FCER1A rs539959920 C > T and PLCG2 rs72832034 C > T-were consistently associated with poorer OS (adjusted HR = 1.19, 95% CI = 1.04-1.37, p = 0.014; HR = 1.34, 95% CI = 1.09-1.64, p = 0.005). Patients carrying multiple unfavorable genotypes exhibited a dose-dependent decline in survival (P = 0.002). Incorporation of these SNPs modestly improved time-dependent AUCs for OS prediction at 36 months. Single-cell expression and splicing QTL analyses demonstrated allele-specific modulation of FCER1A and PLCG2 expression across immune cell subsets, consistent with altered immune infiltration patterns in the GC TME. These findings suggest that two germline variants in FCER1A and PLCG2 independently predict GC survival, likely through transcriptional and immunologic modulation, thereby nominating these variants as potential immune-genetic biomarkers for GC prognosis and therapeutic stratification. - Source: PubMed
Publication date: 2026/05/15
Zeng GuangLu GuoqiangHu BeipingXu MidieLi GuanlinWang MengyunQiu LixinCheng LeiZhang RuoxinXu WanghongLiu XiaowenJin GuangfuLiu HongliangWei Qingyi - Obstructive sleep apnea (OSA), a prevalent sleep disorder associated with migraine, has unclear effects on cellular heterogeneity within this comorbid context. - Source: PubMed
Publication date: 2026/05/11
Cen QipengXie YoufengSong WenyiCao TingtingWei QingyanLiang GuiningLiang LucongZou ChunLi RongjiePan MikaSu LiZou Donghua