MN1 and PTEN gene expression in acute myeloid leukemia.

OBJECTIVE: Multiple genetic alterations with prognostic significance have been discovered in acute myeloid leukemia (AML). We studied the expression level of two genes, Meningioma1 (MN1) and Phosphatase and Tensin homolog (PTEN) to determine their expression in AML patients and their role as prognostic markers. METHODS: The study included 50 cytogenetic normal de novo AML cases and 10 controls, Their level was detected by Real time Reverse Transcription-Polymerase Chain Reaction. RESULT: Relative mRNA expression of MN1 was significantly higher (p value < 0.001) and PTEN expression was significantly lower (p value = 0.002). No correlation was found between neither MN1 nor PTEN mRNA expression and overall survival (p value = 0.212 and 0.310) respectively. CONCLUSION: Although our study suggests a role for MN1 gene and PTEN genes in AML, we could not recommend their use as routine diagnostic and prognostic markers for AML in Egyptian population.

Frequency of Hereditary Hemochromatosis (HFE) Gene Mutations in Egyptian Beta Thalassemia Patients and its Relation to Iron Overload.

AIM: This study aimed to detect the most common HFE gene mutations (C282Y, H63D, and S56C) in Egyptian beta thalassemia major patients and its relation to their iron status. SUBJECTS AND METHODS: The study included 50 beta thalassemia major patients and 30 age and sex matched healthy persons as a control group. Serum ferritin, serum iron and TIBC level were measured. Detection of the three HFE gene mutations (C282Y, H63D and S65C) was done by PCR-RFLP analysis. Confirmation of positive cases for the mutations was done by sequencing. RESULTS: Neither homozygote nor carrier status for the C282Y or S65C alleles was found. The H63D heterozygous state was detected in 5/50 (10%) thalassemic patients and in 1/30 (3.3%) controls with no statistically significant difference between patients and control groups (p = 0.22). Significantly higher levels of the serum ferritin and serum iron in patients with this mutation (p = 001). CONCLUSION: Our results suggest that there is an association between H63D mutation and the severity of iron overload in thalassemic patients.

Interleukin-23R gene polymorphism in pediatric Egyptian patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia is an acquired autoimmune disorder caused by the production of antiplatelet antibodies. These autoantibodies opsonize platelets for splenic clearance, resulting in low levels of circulating platelets. The current case-control study aimed at detecting the frequency of interleukin-23 receptor rs1884444 single nucleotide polymorphism in Egyptian children with primary immune thrombocytopenia and its possible role as a genetic marker for disease risk. Interleukin-23 receptor rs1884444 single nucleotide polymorphism was studied in 50 patients with primary immune thrombocytopenia and 100 healthy age and sex-matched controls by polymerase chain reaction amplification of the target gene followed by allele-specific restriction enzyme digestion. Regarding the distribution of the genotypes of the interleukin-23 receptor rs1884444 polymorphism, no statistically significant difference was found between cases and control groups. The variant genotypes (GT/TT) frequency was 10% in primary immune thrombocytopenia cases versus 7% in the control groups [P value = 0.755, odds ratio (OR): 0.326, 95% confidence interval (CI): 0.099-1.076]. Similarly, no difference was found between acute and chronic cases. The variant genotypes GT/TT frequency was 10.7% in acute versus 9.1% in chronic primary immune thrombocytopenia (P value = 0.849). The variant genotypes GT/TT were not found to be a risk factor for acute primary (P value = 0.807, OR: 0.641, 95% CI: 0.16-2.563) or chronic primary immune thrombocytopenia (P value = 0.914, OR: 0.762, 95% CI: 0.153-3.797). Our study suggests the possibility that interleukin-23 receptor gene polymorphism may not contribute to the susceptibility of development of primary immune thrombocytopenia in Egyptian children.

Detection of expression of IL-18 and its binding protein in Egyptian pediatric immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder, characterized by dysfunctional cellular immunity including the presence of activated platelet specific autoreactive T cells that recognize and respond to autologous platelet antigens. Autoreactive T cells drive the generation of platelet reactive autoantibodies by B cells as well as T-cytotoxic cell-mediated lysis of platelets. Interleukin-18 (IL-18) is a mediator of T helper type 1 cell responses synergistically with IL-12 that initiate and promote host defense and inflammation. IL-18 has a specific binding protein (IL-18BP) which belongs to the immunoglobulin superfamily. In the present study, serum level and messenger RNA( mRNA) expression of IL-18 as well as IL-18BP mRNA expression were measured in peripheral blood mononuclear cells (PBMNCs) of 100 Egyptian pediatric patients with ITP (70 acute and 30 chronic). In addition to this, we recruited 80 healthy volunteers in order to investigate the possible association between the imbalance of IL-18 and IL-18 BP expressions and the pathogenesis of ITP. IL-18 serum level and mRNA expression were not elevated in cases more than in the control group, but IL-18 mRNA was higher in chronic cases when compared to the acute ones (p=0.031) and there was a good negative correlation between the platelet count and serum IL-18. IL-18 BP m-RNA was slightly elevated in cases more than in the control group (95% Confidence interval=1.15-2.01). Our results were not supportive for previous findings of elevated IL18/BP mRNA ratio in ITP patients. This could be referred to the fact that autoimmune diseases are complex genetic disorders, therefore further studies on polymorphisms affecting IL-18 gene expression as well as kinetics of IL-18 expression are required to evaluate the role of interleukin 18 and its binding protein in the pathogenesis of ITP.

Immunoregulatory cytokines gene polymorphisms in Egyptian patients affected with acquired aplastic anemia.

The immune system is thought to play an important role in aplastic anemia (AA) in light of recent findings of hematologic reconstitution after immunosuppressive therapy. T cell activation, apoptosis, and the cytokines interferon- and TNF-α are suspected to play a role in the suppression of growth of progenitor cells and induced apoptosis in CD34 target cells, TGFß is a multifunctional peptide, usually produced in latent form and requiring activation to produce a biological response. Also, TGF-ß1 has been described as an important negative regulator of haemopoiesis. Over production of IL-6 is described in AA but is of unknown pathophysiological significance. To investigate the role of cytokine gene polymorphisms (IL-6/-174, TNF-α/-308, IFN-γ/+874, and TGFß1/-509) in patients with acquired AA to assess if genotypes associated with higher or lower production were more prevalent than in established control population and to study the possible association of these genotypes with the disease severity. Fifty AA patients were included in this study. Polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) technique was used to detect INF-γ single nucleotide polymorphism -874A/T, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to assess IL-6-174 C/G, TNF-α-308G/A, and TGFb1-509C/T gene polymorphisms. Genotypes associated with high production of TNF-α, TGF-ß and IFN-γ, and IL-6 were more frequent in patients than in control; no association was found between the presence of hypersecretory genotypes and the disease severity.