Publications by authors named "Mostafa F Mohammed Saleh"

2 Publications

  • Page 1 of 1

Up-regulation of regulatory T cells, CD200 and TIM3 expression in cytogenetically normal acute myeloid leukemia.

Cancer Biomark 2018 ;22(3):587-595

Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt.

Background: The bone marrow immunosuppressive microenvironment of AML patients sustains and modulates proliferation, survival and drug resistance of AML through deregulation of both innate and adaptive immune response. We aimed to investigate the level of Tregs, expression of Tim-3 on peripheral blood T cells, expression of CD200 in myeloid blasts in newly diagnosed AML patients with normal cytogenetics (AML-NC) and their prognostic impact.

Patients And Methods: This study included 40 patients with de novo AML-NC and 20 healthy controls. Flow-cytometry was used for detection of CD4+CD25+high FoxP3+ regulatory T cells, Tim-3 expression on peripheral blood T cells and CD200 expression on myeloid blasts.

Results: The percentages of CD4+CD25+high and CD4+CD25+high Foxp3+ Tregs were significantly increased in AML patients than controls. The levels of Tregs, Tim-3/CD4+, Tim-3/CD8+, CD200 and MFI of CD200 were significantly lower in responding patients than in those with persistent leukemia. Only high CD200 expression (> 50%) showed statistically significant worse OS with P< 0.04.

Conclusion: The increased levels of Tregs, Tim-3 expression on peripheral blood T cells and CD200 expression in myeloid blast in AML patients could play a role in the development of AML. Analysis of these markers could serve as prognostic markers and might guide the therapy in AML patients in the future.
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http://dx.doi.org/10.3233/CBM-181368DOI Listing
October 2018

The impact of cytokine gene polymorphisms on the outcome of HLA matched sibling hematopoietic stem cell transplantation.

Cytokine 2018 10 24;110:404-411. Epub 2018 May 24.

Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt; Bone Marrow Transplantation Unit, Nasser Institute Hospital for Research and Treatment, Cairo, Egypt.

Graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell transplantation (HSCT); cytokines are recognized as important mediators in its pathogenesis. In this study we investigated the role of cytokine gene polymorphisms on HSCT outcome. A total of 106 patient and 98 donors were genotyped by polymerase chain reaction sequence specific primers (PCR-SSP) based assay for tumor necrosis factor-α-308 (TNFα -308), interleukin (IL)-6-174, IL-10-1082, -819, -592, Interferon-γ+874 (IFN-γ+874), and transforming growth factor-β1 (TGF-β1) codon10 and 25 polymorphisms. Except one in each category, all patients and donors were TNFα -308 high producers and the majority were IL-6-174 high producers (93.3% and 90.8% respectively); a pattern that would alleviate any potential biological impact. Patient's IFN-γ+874 showed significant association with the development of chronic GVHD. Patients with IFN-γ +874 high producer showed an 8 folds likelihood to develop chronic GVHD as compared to those with IFN-γ+874 low producer predicted phenotype (95% CI: 1.59-40.2, p = 0.01). Patient's TGFβ1-codon 10 and 25 high/intermediate producers showed a lower incidence of acute GVHD though it did not achieve statistical significance (p = 0.065) on account of the low frequency of this genotype in our patients and donors (11.4 and 8.2% respectively). Other factors contributing to risk of GVHD included older age for both acute and chronic (p = 0.01 and 0.02 respectively) with age 24 as the best discriminating cutoff; CD34+ cell dose for chronic GVHD (p = 0.045) with a dose of 8 × 10/kg as the best discriminating cutoff; and conditioning regimen with Flu/Bu associated with the lowest incidence of acute GVHD (p = 0.003) and no impact on chronic GVHD. In conclusion the current study further indicates a potential role of some cytokine gene polymorphisms in the development of GVHD. The relative distribution of high and low producer genotypes in different ethnic groups contributes to their biological impact in different populations.
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http://dx.doi.org/10.1016/j.cyto.2018.05.003DOI Listing
October 2018