IKZF1 antibody - middle region (ARP31470_P050)
- Known as:
- IKZF1 (anti-) - middle region (ARP31470_P050)
- Catalog number:
- arp31470_p050
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- IKZF1 antibody - middle region (ARP31470_P050)
Related genes to: IKZF1 antibody - middle region (ARP31470_P050)
- Gene:
- IKZF1 NIH gene
- Name:
- IKAROS family zinc finger 1
- Previous symbol:
- ZNFN1A1
- Synonyms:
- hIk-1, LyF-1, Hs.54452, IKAROS, PPP1R92
- Chromosome:
- 7p12.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-08-23
- Date modifiied:
- 2019-04-23
Related products to: IKZF1 antibody - middle region (ARP31470_P050)
Related articles to: IKZF1 antibody - middle region (ARP31470_P050)
- Based on the tumor Warburg effect and the strategy of GLUT-mediated drug transport, we have successfully discovered a promising molecular glue immunomodulatory drug (IMiD) candidate that exhibits excellent dual-targeting capability in tumor selective drug uptake, immunotherapy and combating lenalidomide (LEN) and pomalidomide (POM) resistance in multiple myeloma. The structure-activity relationship study culminated in the identification of the lena- and pomalidomide-glycoconjugates (1 and 20) with potent antitumor activity in cancer cells overexpressing GLUT1, especially in the highly resistant human multiple myeloma to LEN and POM. Compound 20 could completely counteract the resistance of MM.1S cells to LEN and POM with resistance indices were reduced by 100- and 550-fold, respectively. It also achieved 60.5% tumor growth inhibition (TGI) (vs. 26.9% for POM) in a MM.1S/POM drug-resistance xenograft model. Mechanistic studies demonstrated that 20 could GLUT1-dependently accumulate in tumor cells and exert antitumor effects as molecular glue by inducing IKZF1 and CK1α degradation. - Source: PubMed
Publication date: 2026/07/28
Jia ManweiZhang RuLiu YangGao XiangqianLi ZhiyiXu JunLiu ShengnanGao Qingzhi - B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy occurring in children and a leading cause of cancer-related mortality, thus there is an urgent need for development of novel therapeutic strategies for high risk B-ALL patients. The significance of gene alterations in B-ALL cases is controversial, as some studies have shown those to be associated with poor prognosis, while others have reported that deletion of exons 4-7 of the gene, which results in generation of IKAROS isoform 6, is related favorable prognosis. For the present study, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 was employed for knockout of the gene and various IKAROS knockout lines were established, which allowed for investigation of precise functions of the gene by comparing four lines with different IKAROS isoform 1 and 6 statuses. The results clearly showed induction of significant differentiation and cell cycle progression in IKAROS isoform 6 knockout clones. Furthermore, knockout of IKAROS isoform 6 resulted in significant upregulation of the expression of IKAROS isoform 1 as well as signal transducer and activator of transcription 5 (STAT5) activity, which are considered to be related to the observed features. Further investigations are warranted to provide greater mechanistic insight regarding IKAROS-mediating pathways, which will lead to development of novel therapy for human B-ALL. - Source: PubMed
Ogimoto YuyaKawachi-Nakamura MarikoHashimoto KazunoriYanagisawa Kiyoshi - B-cell precursor acute lymphoblastic leukemia (preB-ALL) is characterized by pathogenic variants currently used in precision oncology. However, the mutational landscape of Mexican children with preB-ALL has not yet been thoroughly explored and defined in terms of the clinical significance. We used a custom-designed next-generation sequencing exome panel, along with high-resolution chromosome microarrays and gene fusion-targeted assays, to characterize the mutational landscape of 73 Mexican children with preB-ALL, exploring the profile of clinically significant variants. We classified the variants following the AMP-ASCO-CAP 2017 and ACMG-CG 2019 guidelines recommendations. The mutational landscape includes a broad molecular spectrum of variants affecting cell cycle regulation, B-cell development, kinase signaling, and epigenetic regulation genes. Tier 1 diagnostic variants allowed the identification of pre-B ALL genetic subtypes, diminishing the preB-ALL NOS group from 63% to 37%. Furthermore, 37% of cases presented Tier 1 variants conferring intermediate to adverse prognoses (primarily involving CRLF2 gene fusions, as well as PAX5, IKZF1, and TP53 inactivating mutations). Notably, these patients exhibited high-risk clinical features and a lower event free survival rate than patients without these variants (60% versus 41.2%; p = 0.046; 95% CI). Between 19% and 42% of patients had Tier 2 variants targetable with JAK-STAT or RAS-MAPK signaling inhibitors. These patients showed a lower overall survival rate than patients without these variants (64% versus 90%; p = 0.048; 95% CI). Tier 1 potential germline variants in cancer predisposition genes (mainly BRCA1/2 and CHEK2) were observed in 10% of patients, some of whom had a family history of cancer. This highlights the importance of genetic counseling for patients and their families. Finally, 33% of patients had Tier 3 variants that were predicted to be deleterious and potentially upgraded to pathogenic with plausible clinical relevance. In conclusion, the mutational landscape analysis revealed variants useful for oncologic management and genetic counseling of Mexican children with preB-ALL. - Source: PubMed
Martínez Anaya DanielJuárez-Velázquez María Del RocíoJuárez Figueroa UlisesDean MichaelSalas Labadía ConsueloValladares Coyotecatl MarianReyes León AdrianaLópez Santiago NormaJuárez Villegas LuisZapata Tarrés MartaPérez-Vera Patricia - This study aimed to evaluate the feasibility of CD72 as a complementary CD19-independent B-lineage gating marker for longitudinal measurable residual disease (MRD) surveillance in relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) following CD19 CAR-T therapy. Correlation analyses were performed in 66 B-ALL samples to compare MRD detection using CD72, CD19, and cytoplasmic CD79a. CD72 expression specificity was further evaluated in 129 leukemia patients. In addition, 129 patients with R/R B-ALL treated with autologous CD19 CAR-T therapy in registered clinical trials (ChiCTR-IIh-16008711; NCT03173417) between January 2021 and December 2022 were retrospectively analyzed, with follow-up continued until January 2025. CD72 gating showed excellent concordance with both CD19- and cCD79a-based strategies for MRD assessment. CD72 expression demonstrated high specificity in B-ALL, with a positivity rate of 95.77%, compared with 29.27% in AML and 23.53% in T-ALL. All 129 heavily pretreated patients achieved MRD-negative CR at day 28 after CAR-T infusion and subsequently underwent allo-HSCT, with a median interval of 54 days (range, 40-338). A total of 16 patients experienced MRD relapse during follow-up, including four clinically confirmed CD19-negative relapses that retained CD72 expression. Patients with pre-CAR-T MRD ≤1% showed earlier B-cell recovery than those with MRD >1% (median 30 [18-45] vs. 32 [26-79] days, p = 0.028). The MRD ≤1% cohort demonstrated significantly improved 3-year overall survival compared with the MRD >1% cohort (88.1% vs. 69.2%, p = 0.014). The 3-year cumulative incidence of MRD relapse was significantly lower in the MRD ≤1% cohort than in the MRD >1% cohort (3.96% vs. 17.95%, p = 0.019), while non-relapse mortality was also numerically lower in the MRD ≤1% cohort (5.92% vs. 17.95%, p = 0.053). Multivariate analysis identified KMT2A rearrangement, IKZF1 mutation, TP53 mutation, and elevated pre-CAR-T MRD as independent predictors of inferior outcomes. CD72 represents a feasible complementary B-lineage marker for longitudinal MRD surveillance following CD19 CAR-T therapy. Retention of CD72 expression in clinically confirmed CD19-negative relapses supports its potential utility when CD19 expression is lost after targeted therapy. - Source: PubMed
Publication date: 2026/08/03
Chen ManZhou JingZhao WeiLong JingFu MinjingZhang XianLi YiZhang GailingWang Hui - Immunomodulatory drugs such as thalidomide and its derivatives act as molecular glues by binding to the E3 ligase substrate receptor cereblon (CRBN) and promoting the selective recruitment and degradation of specific neosubstrates. Despite extensive structural and experimental characterization, the molecular origin of ligand-induced neosubstrate selectivity remains incompletely understood. Here, we present a comparative computational study of ternary CRBN-ligand-neosubstrate complexes involving two biologically relevant neosubstrates, IKZF1 and SALL4, and five thalidomide derivatives displaying distinct experimental selectivity profiles. Using molecular dynamics simulations and thermodynamic integration calculations, we analyze ligand binding poses, CRBN-ligand interactions, and protein-protein contacts within the ternary complexes. Our results show that all ligands bind CRBN through a conserved interaction network within the thalidomide-binding domain, while direct and persistent ligand-neosubstrate contacts are not observed for the most stable binding modes. Moreover, the CRBN-neosubstrate interaction patterns remain largely unchanged across ligands, and calculated relative binding free energies do not reproduce experimentally observed selectivity trends. These findings suggest that ligand-induced selectivity cannot be explained solely by static interaction patterns in the ternary complex and point to the importance of additional factors, such as CRBN conformational dynamics and kinetic effects, in controlling neosubstrate recruitment. - Source: PubMed
Publication date: 2026/07/13
Martín VerónicaAndjelkovic MiloradBarrientos CarmenLeon IkerTuñón Iñaki