WT1 overexpression

In conclusion, the -700 to 0 bp region is the key region of the JUN promoter, with WT1 inhibiting JUN transcription. The results of the study not only provide ideas for exploring the regulatory mechanism of JUN in chicken SSCs, but also lay an important foundation for the study of avian SSCs.

We confirmed that MRD status prior to alloHSCT is a strong prognostic factor for OS, DFS and CIR. Combining MFC and molecular-PCR techniques to assess MRD seems primordial as inter-method discordance can be consequential.

WT1 expression levels may serve as a valuable ancillary marker in MRD assessment and relapse prediction post-allo-SCT in AML patients, particularly for those lacking specific fusion genes or mutations. However, further large-scale, controlled studies are needed to standardize WT1 MRD assays and establish clear guidelines for their clinical application.

DRI and WT1 expression associate significantly with OS after AZA/DLI. Hence, WT1 may represent an MRD marker, especially in CR patients at high risk.

WT1MRD response post-intensification I serves as an independent prognostic factor for survival in pediatric AML. Integration of WT1 and MFC-based MRD results enhances the reliability of MRD-based prognostic stratification, particularly in patients lacking specific leukemic markers, thereby influencing treatment strategies.

Interestingly, this overexpression was observed in all molecular subtypes of invasive breast cancer, underscoring the significance of WT1 as a potential target in all these subtypes. The observed WT1 down-expression in a few cases of invasive breast cancer, associated with better survival outcomes, may correspond to the down-regulation of a particular WT1-KTS (-) isoform: the WT1 A isoform (EX5-/KTS-). The co-expression of this WT1 oncogenic isoform with a regulated WT1- tumor suppressor isoform, such as the major WT1 F isoform (EX5-/KTS +), could also explain such survival outcomes. Due to its capacity to adopt dual roles, it becomes imperative to conduct individual molecular expression profiling of the WT1 gene. Such an approach holds great promise in the development of personalized treatment strategies for breast cancer.

Furthermore, CCND2 elevation partially offsets the impacts of miR-186-5p elevation on Aβ1-42-stimulated cell proliferation as well as apoptosis mediated with WT1-AS up-regulation. Our results indicated that up-regulation of lncRNA WT1-AS ameliorated Aβ-stimulated neuronal damage through modulating miR-186-5p/CCND2 axis, offering a novel direction for AD therapy.

In B-other patients, WT1 overexpression at diagnosis predicted an inferior prognosis. The WT1 gene may serve as a biomarker for monitoring residual disease in the B-other population, especially in children in the standard-risk group.

These results confirm that qPCR targeting NPM1 mutations or fusion transcripts are superior in MRD testing. In the absence of such targets, ddPCR is a promising alternative demonstrating (a) high applicability, (b) high sensitivity, and (c) zero false positive MRD relapses in non-relapsing patients.

Finally, we show that ESK-1, a T cell receptor-like monoclonal antibody that recognizes WT1 peptides presented on MHC HLA-A0201, shows increased binding to endothelial cells after KSHV infection or induction of vFLIP expression. We propose that oncogenic isoforms of WT1 are upregulated by KSHV to promote tumorigenesis and that immunotherapy directed against WT1 may be an approach for KS treatment.

Idarubicin + Cytarabine (IA) regimen could reduce the expression level of WT1 after treatment, and Allo-HSCT played an important role in improving the prognosis of patients with WT1 high expression and patients with WT1 negativity. Different clinical background should be taken into consideration when we judge the prognosis and therapeutic effect of patients with WT1 mutations. In addition, WT1 may be an optional MRD marker, which needs regular monitoring.

A total of 27 (7.6%) MDS/CMML patients with trisomy 8 (21 with trisomy 8 at baseline) were found to have a bona fide autoimmune disease, including autoimmune uveitis/scleritis (n=3), (rheumatoid and psoriatic), polyarteritis nodosa, giant cell arteritis with polymyalgia rheumatica, autoimmune sclerosing pancreatitis, immune hemolytic anemia, synovitis, and Grave's disease. Conclusions MDS/CMML with trisomy 8 showed unique clinicopathologic characteristics compared to MDS-NK: higher baseline BM blasts, higher representation of "Very High" IPSS-R risk categories with characteristic mutational signatures and a variety of underlying autoimmune diseases.

Moreover, subcutaneous injections of M-WIP2W were observed to significantly enhance intra-tumoral accumulation and to effectively inhibit tumor growth. Thus, WIP2W stands out as a potent and selective WT1 inhibitor, and the M-WIP2W nanoformulation appears promising for the therapeutic treatment of refractory CML as well as other WT1-overexpressing malignant cancers.

Many researchers were interested in developing WT1 targeting therapy. In this review, we summarized biological and pathological functions, correlation with other genes and clinical features, prognosis value and targeting therapy of WT1 in hematological features.

Functionally, inhibition of the nonsense-mediated mRNA decay machinery revealed that under natural conditions, the mutated WT1 alleles go through a robust degradation. These results offer new insights and model systems regarding the characteristics of WT1 in leukemia and lymphoma.

This research revealed higher WT1 expression in PTL relative to nodal DLBCL, suggesting that a specific miRNA subset may target WT1 expression and impact the PI3k/Akt pathway in PTL. Further investigation is needed to explore WT1's biological role in PTL and its potential as a therapeutic target.

PV patients with different JAK2 gene mutational status had various clinical characteristics. JAK2 V617F allele burden was positively correlated with the age of onset, leukocyte counts and lactate dehydrogenase values. WT1 gene is overexpressed in PV, and the expression level of WT1 was positively correlated with JAK2V617F allele burden.

MRD assessment by WT1 can be used as a sensitive tool for prediction of the clinical outcome in pediatric patients with AML. Incorporation of MRD results by both WT1 and MFC enhanced the reliability of MRD-based prognostic stratification especially in patients without specific markers to be followed and hence influence the treatment strategies.

In MDS patients, the proportion of CD3T and CD4T lymphocytes decreased, and the proportion of activated T cells increased, indicating that the differentiation type of MDS is more primitive and the prognosis is worse.

In multivariate analysis, higher WT1 expression was a risk factors for OS in EB patients without TP53 mutations. Overall, WT1 expression was useful to predict prognosis for MDS and its prognostic role was impacted by some gene mutations.

In conclusion, WT1-AS weakened the stem cell-like behaviors and characteristics of GCSCs in vitro and in vivo by down-regulating WT1. Investigations into the molecular mechanisms underlying the complex phenotypes of GCSCs might contribute to the better management of gastric cancer.

In the survival study, L-WT1 treatment could significantly delay the death of the animals. This work demonstrates the efficacy of the L-siRNA respiratory administration as a novel therapy to reduce pulmonary tumors and to increase survivability by silencing specific cancer oncogenes as WT1.

This work demonstrates the efficacy of the neutral DOPC liposomal-siRNA delivery system by respiratory administration as a novel therapy to reduce the malignancy of pulmonary tumors and to increase survivability by silencing specific cancer biomarkers as WT1.

Finally, we found that the regulation of Wt1 (+/-KTS) variants on the proliferation and migration of HOSEpiC may act through different genes and signaling pathways and screened out key genes and differentially regulated genes that regulate the malignant transformation of ovarian epithelial cells. The implementation of this study will provide new clues for the early diagnosis and precise treatment of OC.

Moreover, WT1-H patients had a significantly lower RFS rate than WT1-L patients within both FAB-M5 and KMT2A rearrangement subgroups (P = 0.010 and 0.028), whereas WT1 had no impact on RFS within other subgroups mentioned above (all P > 0.05). Therefore, high WT1 expression at diagnosis independently predicted induction chemotherapy failure in AML patients with non-favorable cytogenetic risk, and it was related to relapse just within FAB-M5 and KMT2A rearrangement subgroups.

shikonin can down-regulate the WT1 protein level for leukemia differentiation therapy, and 2. the interaction between WT1 and CD34 proteins may be responsible for granulocyte/monocyte immaturity in HL-60 cells.

WT1 may represent a novel target of ART in cancer cells that contribute to the response of tumor cells to this drug.

In the homogeneously treated ALFA-0702 population, MRD-NGS positivity after the first induction course predicts shorter LFS and OS independently of ELN17 risk stratification. Detection of a higher number of mutations in CR is associated with a worse prognosis. Contrary to previous studies accruing older patients treated less intensively persistence of DTA mutations has similar prognostic relevance than non-DTA mutations.

Similarly, transfection with the miR-186-5p inhibitor reduced OGD-induced neuronal damage by upregulating XIAP expression. In conclusion, lncRNA WT1-AS attenuates hypoxia/ischemia-induced neuronal injury in cerebral ischemic stroke through the miR-186-5p/XIAP axis.

Our results demonstrated that the overexpression of WT1 upregulates IL-24, leading to G2/M checkpoint arrest to reduce proliferation. These results indicate that regulation of IL-24 by WT1 inhibits proliferation and may represent a potential target for treating renal carcinoma.

These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of "CIC-rearranged" sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases.

In addition, we provided some practical considerations on how to properly use WT1 expression as an MRD marker, considering its strengths and weaknesses. In order to achieve the best sensitivity and specificity, it is recommended to refer to the standardized method of European LeukemiaNet and its defined threshold (250 WT1 copies/10 Abelson (ABL) on Bone Marrow-BM and 50 WT1 copies/10 ABL on Peripheral Blood-PB), which has been validated in a large and multicenter cohort of patients and normal controls.

The results of this study indicated that a comprehensive evaluation of BM features, clinical phenotypes, haematologic parameters, and molecular profiles is needed for the accurate diagnosis and treatment of ET, pre-PMF, and overt PMF patients.

The treatment effect of CML patients with NOTCH3, RELN and ASXL1 mutations and more than two gene mutations is poor. CML patients with high expression of WT1 at diagnosis have poor therapeutic effect in the early stage.

A unique WT1-specific TCR showed antigen-specific responses and efficiently killed AML blasts, acute lymphoblastic leukemia blasts, and glioblastoma cells in vitro and in vivo in the absence of off-tumor toxicity. T cells engineered to express this receptor are being advanced into clinical development for AML immunotherapy and represent a candidate therapy for other WT1-expressing tumors.

The difference in WT1 expression between patients with normal and abnormal karyotype was statistically insignificant; (4) WT1 gene expression and its rs16754 variant at diagnosis did not affect AML outcome. WT1 mutation may affect RFS in AML.