scholarly journals Role of the Wilms’ tumor 1 gene in the aberrant biological behavior of leukemic cells and the related mechanisms

2014 ◽  
Vol 32 (6) ◽  
pp. 2680-2686 ◽  
Author(s):  
YAN LI ◽  
JIYING WANG ◽  
XIAOYAN LI ◽  
YUJIAO JIA ◽  
LEI HUAI ◽  
...  
2018 ◽  
Author(s):  
Jingjing Wang ◽  
Jinmei Li ◽  
Yunzhao Gu ◽  
Qin Xia ◽  
Weixiang Song ◽  
...  

AbstractAndrogen signaling plays a pivotal role in spermatogenesis, but the molecular mechanisms underlying androgen action in this process are unclear. Specifically, it is unknown if the androgen receptor (AR) is expressed in germ cells. Thus it’s interesting to reveal how androgen induces differentiation of spermatogonial progenitor cells (SPCs) in the niche. Here we observed the AR is primarily expressed in pre-spermatogonia of mice 2 days post partum (dpp), absent before spermatogenesis onset, and then expressed in surrounding Sertoli cells. Then we examined a regulatory role of the AR in spermatogenesis using a SPCs-Sertoli cells co-culture system, and demonstrated that androgen negatively regulated Plzf (the gene for stemness maintenance of SPCs). Additionally, we identified Gata2 as a target of AR in Sertoli cells, and demonstrated that Wilms tumor 1 (WT1) and β1-integrin as two putative intermediate molecules to transfer differentiation signals to SPCs, which was further verified using androgen pharmacological-deprivation mice model. These results demonstrate a regulatory pattern of androgen in SPCs niche in an indirect way via multiple steps of signal transduction.


2018 ◽  
Vol 92 (6) ◽  
pp. 2119-2135 ◽  
Author(s):  
Miriam Pons ◽  
Claudia M. Reichardt ◽  
Dorle Hennig ◽  
Abinaya Nathan ◽  
Nicole Kiweler ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5237-5237
Author(s):  
Hala Abalkhail ◽  
Hassan El-Solh ◽  
Amal Alseraihy ◽  
Mouhab Ayas ◽  
Ali Al-Ahmari ◽  
...  

Abstract Abstract 5237 The synonymous single nucleotide polymorphism rs16754 in the Wilms Tumor-1 gene (WT1) has been reported to correlate with outcome in adult patients with acute myeloid leukemia (AML) when treated with intensive chemotherapy. Specifically the GG genotype is significantly associated with favorable outcome, but also the AG genotype has been reported to be associated with better outcome as well. The clinical relevance of the rs16754 SNP in pediatric AML patients is far from clarified. In addition, it is not known whether allogeneic hematopoietic stem cell transplantation (HSCT) can modify the role of this SNP and its association with outcome. Methods: Genotyping of the SNP by direct sequencing of the exon 7 was performed on bone marrow samples from 86 AML patients (38 pediatrics and 48 adults). All patients were treated with HSCT. Most patients (39 adults and 28 pediatrics) were transplanted in first remission (CR1). The median age was 25 years (range: 14–54) for adults and 8 years (range: 8 months–14 years) for the pediatric group. Results: In pediatric AML, we detected the AA genotype in 22 patients (53%), the GG genotype in 2 patients (5%) and the remaining (42%) had AG genotype. In the adult patients, the AA genotypye was present in 26 patients (54%), GG genotype in 3 (6%) patients, and the AG genotype in the remaining patients (39%). A similar distribution was observed in the normal population (58%, 12%, 30%, for AA, GG, and AG, respectively). In pediatric patients, the AG genotype significantly correlated with shorter overall survival (OS) (P=0.04) and event free survival (EFS) (P=0.04) when compared with the patients with AA genotype. In contrast, in adult AML, groups with AG and AA geneotypes completely overlapped for OS and EFS. When only patients treated with HSCT in CR1 were considered, the pediatric patients showed the same trend (P=0.07), but there was no correlation with survival in the adult group. This analysis included patients with intermediate and adverse risk cytogenetics. AG genotype was not a predictor of outcome in multivariate model incorporating cytogenetics and the WT1 genotype. The patients with the GG genotype were too few for analysis. Conclusion: This data supports the concept that the biology of AML in pediatric patient is different from that in adults. The role of this synonymous SNP in AML needs further exploration, especially investigating the potential that this SNP may have some effects on the host and not only the disease. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 14 (3) ◽  
pp. 2823-2831 ◽  
Author(s):  
Li-Sheng Wu ◽  
Jia-Yi Qian ◽  
Minghai Wang ◽  
Haiwei Yang

JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 1005-1009 ◽  
Author(s):  
D. J. Fernbach
Keyword(s):  

Author(s):  
A.J. Mia ◽  
L.X. Oakford ◽  
T. Yorio

Protein kinase C (PKC) isozymes, when activated, are translocated to particulate membrane fractions for transport to the apical membrane surface in a variety of cell types. Evidence of PKC translocation was demonstrated in human megakaryoblastic leukemic cells, and in cardiac myocytes and fibroblasts, using FTTC immunofluorescent antibody labeling techniques. Recently, we reported immunogold localizations of PKC subtypes I and II in toad urinary bladder epithelia, following 60 min stimulation with Mezerein (MZ), a PKC activator, or antidiuretic hormone (ADH). Localization of isozyme subtypes I and n was carried out in separate grids using specific monoclonal antibodies with subsequent labeling with 20nm protein A-gold probes. Each PKC subtype was found to be distributed singularly and in discrete isolated patches in the cytosol as well as in the apical membrane domains. To determine if the PKC isozymes co-localized within the cell, a double immunogold labeling technique using single grids was utilized.


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