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- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: acute myeloid leukemia,Glutathione peroxidase 3 (GPX3), hematologic malignancies, prognosis
- چکیده:
- چکیده انگلیسی: Background: The impact of low expression of Glutathione peroxidase 3 (GPX3) on the clinical course of acute myeloid leukemia (AML) is poorly investigated. Aims: To explore the status of GPX3 expression and analyze its clinical characteristics and prognosis in a cohort of Egyptian patients with AML. Methods: GPX3 mRNA level was assessed by RT-q PCR in 40 newly diagnosed AML patients and 10 healthy controls. Results: The gene expression level was significantly lower in AML patients than the control group (P < 0.001). A cut off value (0.1223) for the discrimination between AML and controls was obtained by ROC curve. According to this cutoff value; the patients were reassigned into 2 groups; 28 patients with lower GPX3 expression and 12 patients with high GPX3 expression. GPX3low expression was significantly associated with higher incidence of induction death (P= 0.037) and lower CR rate (P=0.048). Moreover, GPX3low expression was significantly associated with shorter cumulative 1-year overall survival (OS) (P = 0.001) and disease-free survival (DFS) (P=0.028). Conclusion: GPX3low expression status is considered a poor prognostic factor in AML predicting shorter OS and DFS. The study highlights the importance of targeting glutathione metabolism as a central component of the anti-leukemia therapy.
- انتشار مقاله: 25-04-1399
- نویسندگان: Yasmine Shaaban,Salah Aref,Mona Taalab,Mohamed Ayed,Mohamed Mabed
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: AML,polymorphisms,TLR4,TLR2
- چکیده:
- چکیده انگلیسی: Backgrounds: Toll-like receptors 2; 4 (TLR2;4) are an essential component of the innate immunity and play an important role in immune-surveillance and immune response to various microorganisms. This study aimed to investigate the association between TLR2 and TLR4 polymorphism and the risk of acquiring severe infections, and impact on AML patient’s outcome. Subjects and methods: Using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP); we analyzed three SNPs in the TLR2 (Arg753Gln) and TLR4 (Asp299Gly and Thr399Ile) in 120 AML patients and 100 healthy control subjects. Results: No significant differences in genotype or alleles frequency between healthy controls and AML patients regarding TLR2 Arg753Gln, TLR4 Asp299Gly and TLR4 Thr399Ile polymorphisms (P>0.05 for all). Neutropenic fever was detected in 110 out of 120 (91.7%) of the studied AML patients. The sepsis and pneumonia were identified in 20 out of 120 patients (16.7%). The incidence of sepsis was associated with TLR2 Arg753Gln: AG genotypes, A allele and TLR4 Asp299Gly: CT genotype and C allele as compared to other genotypes and alleles. Moreover; TLR2 (Arg753Gln) GG polymorphisms significantly associated with shortest overall survival (OS) and shortest disease-free survival (DFS); while TLR4 polymorphisms affect the DSF only but not OS. In AML patients TLR2 Arg753Gln gene polymorphism is associated with high susceptibility to sepsis and TLR4 (Asp299Gly and Thr399Ile) gene polymorphism is associated with high susceptibility for both pneumonia; and sepsis. Conclusion: TLR2 Arg753Gln (AG; GG genotype) polymorphisms are associated with shortest OS and DFS. Moreover; significant association between TLR2 polymorphisms, TLR4 Arg753Gln polymorphisms and risk of severe infections in AML patients was documented.
- انتشار مقاله: 27-12-1398
- نویسندگان: Salah Aref,AL Shaimaa Mansoura Abd Elmaksoud,Sherin Abd Elaziz,Mohamed Mabed,Mohamed Ayed
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: AML,NK cells,MDS,sTNF-α,sIL32
- چکیده:
- چکیده انگلیسی: Background: Myelodysplastic syndromes (MDS) are complex clonal hemopoietic progenitor cell disorders that result from the evolution of aberrant clones which lead to leukemia. Disorders of the immune system serve important functions in the pathophysiology and progression of this disorder. This study aimed to assess the bone marrow natural killer cells percentage as well as soluble TNF-α and sIL-32 concentration levels in MDS patients. Methods: Bone marrow samples were obtained from 34 MDS; 12 MDS-AML and 10 controls. The percentage of total NK cells and mature NK cells were determined by flowcytometry. Bone Marrow soluble TNF-α and sIL-32 concentration levels were measured by ELISA. Results: The percentage of total NK and mature NK cells were significantly lower in MDS patients as compared to controls (p
- انتشار مقاله: 27-12-1398
- نویسندگان: Salah Aref,Nada Khaled,Abdel Hady Al Gilany,Mohamed Ayed,Tarek Abouzeid,Doaa Attia
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Outcome,CTLA-4,CD200,MDS
- چکیده:
- چکیده انگلیسی: Objective: This study was designed in order to identify the prognostic relevance of CD200 expression and soluble Cytotoxic T-lymphocyte antigen-4 (CTLA-4) levels in myelodysplastic syndrome (MDS) patients. Methods: The study included 57 MDS (37 intermediate and 20 high risk) patients and 10 controls. For all of included patients; CD200 expression was identified by flowcytometry on CD33 positive cells and soluble CTLA-4 (CD152) concentration was determined by ELISA. Results: CD200 positive expression was detected in 32/57 (56.1%) of MDS cases, the mean serum CTLA-4 concentrations were significantly higher in MDS patients as compared to controls (P<0.01). Significant association between high CD200 positive expression; high CTLA-4 concentration levels and MDS risk stages being higher in high risk MDS group as compared to intermediate risk one (P < 0.01). After 36-month follow-up; the subgroup of MDS patients with high expression of CD200; and high serum CTLA-4 concentrations showed high death rate and high frequency of acute myeloid leukemia transformation. Conclusions: CD200 positive expression could be considered as a new prognostic marker for risk stratification of MDS patients. CD200 expression may exert its effect through upregulation of CTLA-4.
- انتشار مقاله: 23-10-1398
- نویسندگان: Salah Aref,Mohamed El Agdar,Ahmed El Sebaie,Tarek Abouzeid,Mohamed Sabry,Lamiaa Ibrahim
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Overall Survival,AML,NOTCH1,mutations
- چکیده:
- چکیده انگلیسی: Background: Although NOTCH-1 gene mutations were reported to contributes to leukemogenesis in lymphocytic leukemias, its role in acute myeloid leukemia (AML) remains unclear. Therefor; this study was designed to determine the prevalence and clinical impact of NOTCH-1 mutations in AML patients. Materials and Methods: In the current study, NOTCH-1 gene mutations were identified in Bone Marrow samples obtained from fifty primary AML patients before start of therapy using Sanger sequencing. Results: NOTCH-1 gene mutations were detected in 6 out of 50 AML cases (12%). The three mutations were (two mutations C7318A in the Pest domain exon 34); (another 2 in the Pest domain Del 7,344, ins C7349, G7356A and the last ones in the HD-N exon-26 (Del A4609). The clinical findings in the mutant AML (mu AML) patients did not significantly different as compared to the un mutated (unmut) AML patients. There is significant association between CD7 aberrant expression and NOTCH-1 mutations. The complete remission was significantly higher in unmut AML cases as compared to mut AML ones (P=0.024). Multivariate (Age; Gender; Bone Marrow Blast cells; NOTCH-1 mutations) Cox regression analysis revealed that NOTCH-1 mutation is an independent risk factor for AML overall survival (P<0.001). The OS in unmut AML group (21.2 months) was significantly longer as compared to mut AML one (1.2 months) (P<0.001). Conclusion: Our data indicate that NOTCH-1 gene mutations were detected in 12% of AML patients. These mutations displayed bad clinical outcome on AML patients. Therapeutic targeting of NOTCH-1 could be a potentially effective approach to combat master oncogenic drivers in AML.
- انتشار مقاله: 21-10-1398
- نویسندگان: Salah Aref,Rasha Rizk,Mohamed El Agder,Wafaa Fakhry,Maha El Zafarany,Mohamed Sabry
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Prognosis,AML,CD56,CD200
- چکیده:
- چکیده انگلیسی: Background: Acute myeloid leukemia (AML) escape from immunosurveillance by immunosuppression. CD200 and CD56 expression represented an independent prognostic factor in many hematological malignancies but its importance in AML patients remains to be identified. Methods: CD200 and CD56 expression were assessed in the bone marrow blasts for Fifty-two (52) newly diagnosed AML by flowcytometry before start of therapy. Results: CD200+ expression was reported in 28.8% of patients while 17.3% of patients showed CD56+ expression. M4 FAB revealed high frequency of both CD200+ and CD56+ expression. The overall survival of CD200+ patients was 19.2% compared to 35.3% in CD200- (P= 0.049). On the other hand, CD56+ patients had the lowest complete remission rate (22.2% vs. 53.4%). In addition, CD56+ population had significant bad influence on overall survival than those of CD56- population (11.1 % vs. 35.5 %, P= 0.047). Conclusions: CD200 and CD56 positive expression by myeloblasts at diagnosis denote poor prognostic indicator and correlated with poor cytogenetic findings. CD200 could be used as therapeutic target in AML.
- انتشار مقاله: 24-08-1398
- نویسندگان: Salah Aref,Nashwa Abousamra,Emann El-Helaly,Mohamed Mabed
- مشاهده