Amir Kahrizi; Armin Akbar; Ahmad Najafi; Hossein Asgarian-Omran; Hossein Karami; Mohammad Naderisorki; Alireza Karimi; Mohsen Tehrani
Abstract
Background: Glucose deprivation in T lymphocytes can trigger compensatory metabolic pathways, potentially contributing to T-cell exhaustion. Additionally, it may induce the unfolded protein response (UPR), ultimately resulting in endoplasmic reticulum (ER) stress.Objectives: To examine the transcriptional ...
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Background: Glucose deprivation in T lymphocytes can trigger compensatory metabolic pathways, potentially contributing to T-cell exhaustion. Additionally, it may induce the unfolded protein response (UPR), ultimately resulting in endoplasmic reticulum (ER) stress.Objectives: To examine the transcriptional profiles of endoplasmic reticulum (ER) stress markers and T-cell exhaustion indicators in CD8+ T lymphocytes isolated from B-ALL patients.Methods: Peripheral blood samples were collected from 22 untreated B-ALL patients and 22 healthy controls. Magnetic Activated Cell Sorting (MACS) was used to isolate CD8+ T lymphocytes. The relative gene expression was then assessed using qRT-PCR with primers specific to XBP1, CHOP, GLUT1, and T-bet.Result: The ER stress response was significantly activated in CD8+ T lymphocytes from B-ALL patients, as evidenced by significant increase in both XBP1 and CHOP transcript levels, relative to normal donors. Although GLUT1 mRNA expression was significantly higher than in control groups, T-bet expression showed no significant difference between the two groups..Conclusion: Collectively, our gene expression data suggest ER stress activation in CD8+ T lymphocytes from B-ALL patients. These findings warrant further investigation into ER stress-related signaling pathways and their potential role in promoting T-cell exhaustion in B-ALL.
Marina Nayeli Medina-Rosales; Susana Godina-Gonzalez; Mariana Haydee Garcia-Hernandez
Abstract
Background: Drugs used in cancer treatment specifically kill T regulatory cells. Objective: To determine different phenotypes of T regulatory cells during the maintenance phase chemotherapy for pediatric acute lymphoblastic leukemia (ALL). Materials: We evaluated the percentages of regulatory T cells ...
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Background: Drugs used in cancer treatment specifically kill T regulatory cells. Objective: To determine different phenotypes of T regulatory cells during the maintenance phase chemotherapy for pediatric acute lymphoblastic leukemia (ALL). Materials: We evaluated the percentages of regulatory T cells by flow cytometry. Soluble CTLA-4 (sCTLA-4) in plasma was evaluated by ELISA assay. Results: Increased percentages of CD4+CD25+ T cells, CD4+CD39+ T cells, CD4+Foxp3+ T cells, and CD4+CD25High T cells were observed in children with ALL in comparison to healthy controls. In addition, the ALL patients with >12 months of therapy showed increased CD4+CD39+ T cells compared to the ALL patients with ≤12 months and healthy controls. Similarly, the CD4+CD25+ T cells and CD4+Foxp3+ T cells increased according to maintenance therapy time. Conclusion: Our results showed increased percentages of regulatory T cells in pediatric ALL patients despite chemotherapy, which might be compromising the anti-leukemic cellular immune response.
Mohammadrasul Zareinejad; Afshin Samiei; Behnaz Valibeigi; Tahereh Gholami; Soheila Zareifar; Zahra Amirghofran
Abstract
Background: Interleukin (IL)-23 has an important role in tumor immune regulation. Objective: To investigate the possible association of interleukin-23 receptor (IL23R) gene variants rs1884444, rs10889677 and rs11209026 with development of acute lymphoblastic leukemia (ALL). Methods: The IL23R variants ...
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Background: Interleukin (IL)-23 has an important role in tumor immune regulation. Objective: To investigate the possible association of interleukin-23 receptor (IL23R) gene variants rs1884444, rs10889677 and rs11209026 with development of acute lymphoblastic leukemia (ALL). Methods: The IL23R variants were studied in 164 ALL patients and compared to 175 healthy controls by polymerase chain reaction-restriction fragment length polymorphism. The relationship between these variants and clinical and laboratory features of the patients and response to therapy were evaluated. Results: No significant differences in genotype and allele frequencies existed between patients and controls. The rs1884444TG genotype was significantly lower in patients who relapsed (24.2%) compared to those without relapse (55.9%, p=0.006). Fewer patients who relapsed had evidence of the G allele (P=0.034). The TG genotype was associated with a longer complete remission at1804±116 days compared to other genotypes (<1217 days, p=0.028), however this result was not significant in multivariate analysis. The rs10889677 AA genotype and A allele was associated with age (p<0.041) and platelet number (p=0.03) in precursor-B cell ALL (B-ALL) patients. Both occurred more frequently in patients aged 2-10 years (63.6% and 66%, respectively) and in those with platelets >100×103μL (68.4% and 52.4%, respectively). Conclusion: Our findings showed a lack of association of the studied polymorphisms with the risk of ALL. The influence of the rs1884444 polymorphism on relapse rate and association of rs10889677 AA genotype with favorable prognostic factors suggest the influence of the studied polymorphisms on ALL response to therapy and prognosis.
Ali Memarian; Parvaneh Vosough; Hossein Asgarian-Omran; Mina Tabrizi; Mahdi Shabani; Fazel Shokri
Abstract
Background: Dysregulation of WNT signaling has been reported in many malignancies. Objective: This study was conducted to investigate the expression pattern of 14 members of the WNT gene family in different immunophenotypic subtypes of ALL. Methods: Semi-quantitative RT-PCR was performed on samples from ...
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Background: Dysregulation of WNT signaling has been reported in many malignancies. Objective: This study was conducted to investigate the expression pattern of 14 members of the WNT gene family in different immunophenotypic subtypes of ALL. Methods: Semi-quantitative RT-PCR was performed on samples from 71 ALL patients and 36 age-matched healthy individuals. The ALL patients were categorized into BALL (76%), T-ALL (22.6%) and mixed lineage (1.4%) and the B-ALL cases were further classified into pro-B, pre-BI, pre-BII and immature/mature-B based on immunophenotypic results. Results: Among the WNT genes, WNT-7B (p=0.026), WNT-9A (p=0.020) and WNT-16B (p=0.023) were significantly over-expressed, whereas WNT- 2B (p=0.033), WNT-5A (p=0.016), WNT-7A (p<0.0001) and WNT-10A (p<0.0001) were down-regulated in B-ALL. Among the T-ALL subtype, however, significant down-regulation of WNT-2B, WNT-5B, WNT-7A, WNT-10A and WNT-11 was evident. Comparison between B-ALL subtypes showed significant over-expression of WNT-7B, WNT-9A and WNT-5B in certain subtypes. Conclusion: Our results suggest contribution of the WNT genes in leukemogenesis of ALL.
