scholarly journals Evaluation of Interleukin-9 Expression as a Potential Therapeutic Target in Chronic Lymphocytic Leukemia in a Cohort of Egyptian Patients

2017 ◽  
Vol 33 (4) ◽  
pp. 477-482 ◽  
Author(s):  
Hadeer A. Abbassy ◽  
Reham A. Aboelwafa ◽  
Omar M. Ghallab
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Therapeutic Target ◽  
Lymphocytic Leukemia ◽  
Potential Therapeutic Target ◽  
Egyptian Patients ◽  
Interleukin 9

scholarly journals Evaluation of interleukin-9 expression as a potential therapeutic target in chronic lymphocytic leukemia in a cohort of Egyptian patients

2017 ◽  
Vol 5 (4) ◽  
pp. 1260
Author(s):  
Hadeer A. Abbassy ◽  
Reham A. Aboelwafa ◽  
Omar M. Ghallab
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Therapeutic Target ◽  
Patient Characteristics ◽  
Lymphocytic Leukemia ◽  
Potential Therapeutic Target ◽  
Protein Levels ◽  
Cd38 Expression ◽  
Zeta Chain ◽  
Egyptian Patients ◽  
Interleukin 9

Background: Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy that has a highly variable clinical course. Genomic features as zeta-chain-associated protein kinase 70 (ZAP70) expression and CD38 expression provide further differentiation of disease prognosis. Extensive studies have confirmed the oncogenic activities of IL-9 in lymphoma. The aim of the current study was to investigate the contribution of IL-9 expression to the pathogenesis of CLL and its correlation to other prognostic parameters.Methods: This study was conducted on 80 patients at diagnosis with CLL and 80 healthy controls. Using real time polymerase chain reaction and enzyme linked immunosorbant assay, IL-9 mRNA expression and its serum level were compared between patients and controls. They were both correlated with other prognostic factors.Results: There was an overexpression of IL-9 in CLL patients that correlated with modified Rai staging, ZAP70, CD38 and all hallmarks of an active and aggressive disease. The correlation between IL-9 upregulation and patient characteristics provided a direct clinical evidence for its contribution to the pathogenesis of CLL.Conclusions: Significantly higher expression of IL -9 measured at both the mRNA and the protein levels in patients with CLL that correlates with more complex course of the disease and worse prognosis may allow one to speculate its importance in the pathogenesis of the disease and its possible role as a potential therapeutic target.

scholarly journals S-MDM4 mRNA overexpression indicates a poor prognosis and marks a potential therapeutic target in chronic lymphocytic leukemia

2012 ◽  
Vol 103 (12) ◽  
pp. 2056-2063 ◽  
Author(s):  
Ling Liu ◽  
Lei Fan ◽  
Cheng Fang ◽  
Zhi-Jian Zou ◽  
Shu Yang ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Therapeutic Target ◽  
Poor Prognosis ◽  
Lymphocytic Leukemia ◽  
Potential Therapeutic Target

Overexpressed BAG3 is a potential therapeutic target in chronic lymphocytic leukemia

2013 ◽  
Vol 93 (3) ◽  
pp. 425-435 ◽  
Author(s):  
Huayuan Zhu ◽  
Wei Wu ◽  
Yuan Fu ◽  
Wenyi Shen ◽  
Kourong Miao ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Therapeutic Target ◽  
Lymphocytic Leukemia ◽  
Potential Therapeutic Target

A Splicing Variant of MDM4 Overexpression Plays an Indicator of p53 Aberrations and Marks a Potential Therapeutic Target in Chronic Lymphocytic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4564-4564
Author(s):  
Wei Xu ◽  
Ling Liu ◽  
Lei Fan ◽  
Li Wang ◽  
Run Zhang ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Therapeutic Target ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Chinese Patients ◽  
Potential Therapeutic Target ◽  
Splicing Variant ◽  
Double Minute ◽  
P53 Status ◽  
Murine Double Minute

Abstract Abstract 4564 Objective Human homolog of murine double minute 4 (MDM4) belongs to murine double minute (MDM) family. Splicing variant of MDM4 (S-MDM4) is obtained from the deletion of exon 6, which results in an internal deletion of 68 bp. Murine double minute 2 (MDM2) is an analogy of MDM4 and shares highly similar structure with each other. The MDM4 gene plays a crucial role in regulating p53 activity and has been found to overexpress in chronic lymphocytic leukemia (CLL). The purpose of this study was to investigate the prognostic significance of MDM4, and characterize the role of MDM4 in p53 pathway. Methods Full-length MDM4 (FL-MDM4), S-MDM4 and MDM2 mRNA expressions were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in 140 Chinese patients with CLL. The correlation between those MDM expressions and CLL prognostic marker such as clinical stage, immunoglobulin heavy-chain variable region (IGHV) mutational status, ZAP-70, CD38, and chromosomal abnormalities were analyzed. Furthermore, primary CLL cells were treated in vitro with either fludarabine or Nutlin-3, to explore the interaction between p53 status and those MDMs. Results FL-MDM4 and S-MDM4 expressions were significantly increased with the del(17p13) (P=0.037 and P=0.006), p53 mutations (P=0.023 and P<0.001) and p53 aberrations (P=0.024 and P<0.001). The correlation between the level of MDM2 expression and p53 status was not observed (P=0.196, P=0.095 and P=0.092, respectively). High level of S-MDM4 mRNA expression was associated with short treatment free survival (TFS) (P=0.004). FL-MDM4 expression was significantly decreased after 24 h treatment with fludarabine (P=0.001), but increased after Nutlin-3-treated (P=0.008) in primary CLL cells without p53 aberrations. Both S-MDM4 and MDM2 expressions were significantly increased after fludarabine-treated in CLL cells without p53 aberrations (P=0.013 and P=0.030). Besides, MDM2 overexpression also occurred in CLL cells with p53 wild type after Nutlin-3-treated (P=0.018). In the primary CLL cells with p53 aberrations or p53 dysfunction, the levels of FL-MDM4, S-MDM4 and MDM2 expressions were not significantly increased or decreased after fludarabine or Nutlin-3 treatment. Conclusion S-MDM4 overexpression is an indicator of p53 aberrations in CLL patients, suggesting those patients have a poor prognosis. FL-MDM4 inhibitory effect on p53 can be removed by MDM2-p53 and saved by Nutlin-3, and S-MDM4 overexpression marks a potential therapeutic target in CLL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Spleen Tyrosine Kinase Is Overexpressed and Represents a Potential Therapeutic Target in Chronic Lymphocytic Leukemia

2009 ◽  
Vol 69 (13) ◽  
pp. 5424-5432 ◽  
Author(s):  
Maike Buchner ◽  
Simon Fuchs ◽  
Gabriele Prinz ◽  
Dietmar Pfeifer ◽  
Kilian Bartholomé ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Tyrosine Kinase ◽  
Therapeutic Target ◽  
Lymphocytic Leukemia ◽  
Spleen Tyrosine Kinase ◽  
Potential Therapeutic Target

scholarly journals Virtual Screening of Adenylate Kinase 3 Inhibitors Employing Pharmacophoric Model, Molecular Docking, and Molecular Dynamics Simulations as Potential Therapeutic Target in Chronic Lymphocytic Leukemia

2021 ◽  
Vol 1 (1) ◽  
pp. 60-79
Author(s):  
Bárbara Lima Fonseca Barbosa ◽  
Tulio Resende Freitas ◽  
Michell de Oliveira Almeida ◽  
Sérgio Schusterschitz da Silva Araújo ◽  
Ana Clara Andrade ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chronic Lymphocytic Leukemia ◽  
Therapeutic Target ◽  
Adenylate Kinase ◽  
Pharmacophore Model ◽  
In Vitro Models ◽  
Lymphocytic Leukemia ◽  
Potential Therapeutic Target ◽  
Docking Simulations

Adenylate kinase 3 (AK3) is an enzyme located in the mitochondrial matrix involved in purine homeostasis. This protein has been considered a potential therapeutic target in chronic lymphocytic leukemia (CLL), because the silencing of the AK3 gene has inhibited cell growth in CLL in vitro models. This study aimed to design potential AK3 inhibitors by applying molecular modeling techniques. Through the mapping of AK3 binding sites, essential interaction fields for pharmacophore design were identified. Online libraries were virtually screened by using a pharmacophore model, and 6891 compounds exhibited the functional groups for interaction with the target. These compounds underwent molecular docking simulations through Surflex and GOLD programs. After visual inspection, we selected 13 compounds for pharmacokinetic properties toxicology prediction via admetSAR and Protox web servers. Finally, six compounds were chosen for further analysis.

Multiple Metamorphoses of CD38 from Prognostic Marker to Disease Modifier to Therapeutic Target in Chronic Lymphocytic Leukemia

2013 ◽  
Vol 13 (23) ◽  
pp. 2955-2964 ◽  
Author(s):  
Tiziana Vaisitti ◽  
Valentina Audrito ◽  
Sara Serra ◽  
Cinzia Bologna ◽  
Francesca Arruga ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Prognostic Marker ◽  
Therapeutic Target ◽  
Lymphocytic Leukemia ◽  
Disease Modifier

scholarly journals DNA-Dependent Protein Kinase Is a Therapeutic Target and an Indicator of Poor Prognosis in B-Cell Chronic Lymphocytic Leukemia

2008 ◽  
Vol 14 (12) ◽  
pp. 3984-3992 ◽  
Author(s):  
Elaine Willmore ◽  
Sarah L. Elliott ◽  
Tryfonia Mainou-Fowler ◽  
Geoffrey P. Summerfield ◽  
Graham H. Jackson ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Therapeutic Target ◽  
Poor Prognosis ◽  
Lymphocytic Leukemia ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Cell Chronic Lymphocytic Leukemia
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