Risk Factors for the Occurrence of Asymptomatic Brain Lesions in Patients with ß-Thalassemia: a Systematic Review and Meta-Analysis.

BACKGROUND: Several factors, including increased platelet aggregation, decreased platelet survival, decreased antithrombotic factors cause a hypercoagulable state in thalassemia patients. This is the first meta-analysis designed to summarize the association of age, splenectomy, gender, and serum ferritin and hemoglobin levels with the occurrence of asymptomatic brain lesions in thalassemia patients using MRI. METHODS: This systematic review and meta-analysis was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. We searched four major databases and included eight articles for this review. The quality of the included studies was assessed based on the Newcastle-Ottawa Scale checklist. Meta-analysis was performed using STATA 13. Odds ratio (OR) and standardized mean difference (SMD) were considered as effect sizes for comparing the categorical and continuous variables, respectively. RESULTS: The pooled OR for splenectomy in patients with brain lesions compared to those without lesions was 2.25 (95% CI 1.22 - 4.17, p = 0.01). The pooled analysis for SMD of age between patients with/without brain lesions was statistically significant, 0.4 (95% CI 0.07 - 0.73, p = 0.017). The pooled OR for the occurrence of silent brain lesions was not statistically significant in males compared to females, 1.08 (95% CI 0.62 - 1.87, p = 0.784). The pooled SMD of Hb and serum ferritin in positive brain lesions compared to negatives were 0.01 (95% CI -0.28, 0.35, p = 0.939) and 0.03 (95% CI -0.28, 0.22, p = 0.817), respectively, which were not statistically significant. CONCLUSIONS: Older age and splenectomy are risk factors for developing asymptomatic brain lesions in ß-thalassemia patients. Physicians should consider a careful assessment of high-risk patients for starting prophylactic treatment.

Selenium Supplementation Alter the Frequency of Th17 but not Th1/Th2 Lymphocytes in Diffuse Large B Cell Lymphoma Patients.

BACKGROUND: Selenium (Se) is a micronutrient, which has recently been proven to have a positive effect on the immune system of cancer patients, but the underlying mechanism is not clearly defined. In this randomized controlled trial, we evaluated the effect of three-month Se supplementation on the profile of CD4+ T-helper subsets including IFN-γ+/IL-4- Th1, IFN-γ-/IL-4+ Th2, and CD4+IL-17+ Th17 cells in sixteen diffuse large B cell lymphoma (DLBCL) patients at stable remission phase who consumed Se (Se+) compared to the fourteen control patients who did not receive Se (Se-). METHODS: The frequency of IFN-γ+/IL-4- Th1, IFN-γ-/IL-4+ Th2, and CD4+IL-17+ Th17 lymphocytes was determined using a four-color flow cytometry method. RESULTS: The results revealed that three-month Se supplementation significantly decreased the proportion of CD4+IL-17+ Th17 lymphocytes but not IFN-γ+/IL-4- Th1 and IFN-γ-/IL-4+ Th2 subtypes in DLBCL patients at stable remission. Change in the percentage of IFN-γ+/IL-4- Th1, IFN-γ-/IL-4+ Th2, and CD4+IL-17+ Th17 cells did not significantly differ between Se+ and Se- groups. No positive correlation was observed between changes in different Th subpopulations in both Se+ and Se- groups. CONCLUSIONS: Taken together, three-month Se supplementation can reduce the proportion of CD4+IL-17+ Th17 cells in DLBCL patients at stable remission phase. Larger population and longer follow-up of patients is necessary to specify the clinical significance of Se supplementation on the popularity of T-helper cells in DLBCL patients.

Investigating the trends of incidence rates of breast cancer in Southern Iran: a population based survey.

BACKGROUND: The overall incidence of breast cancer is different all over the world and even within a nation. The present study aims to investigate the stratum-specific incidence trends of breast cancer in southern Iran. METHODS: In this retrospective cohort study, the data of Fars Population-Based Cancer Registry was used during 2001-2018. New cancer cases with ICD-O-3 codes C50.0 to C50.9 were categorized based on age group, morphology, and topography. Age-specific incidence rates of breast cancer were calculated during 2001-2018. Annual overall and truncated age-standardized incidence rates and their 95% Confidence Intervals (CIs) were also calculated. Afterward, the Annual Percentage Changes (APCs) of the age-specific and age-standardized incidence rates of breast cancer during 2001-2018 were calculated using Joinpoint regression software. RESULTS: An increasing trend was observed in the incidence of breast cancer among women during 2001-2018 (APC of age-standardized incidence rates: 9.5 (95% CI: 7.5, 11.5)).However, the trend was increasing less during the recent years. The APC of age-standardized rates decreased from 15.03 (95% CI: 10.4, 19.8) in 2007 to 6.15(95% CI: 4.0, 8.4) in 2018. The most common morphology of breast cancer was invasive ductal carcinoma (77.3% in females and 75.1% in males) and its trend was similar to the general trend of different types of breast cancer. The most common site of breast cancer was the upper outer quadrant. Most breast cancer cases were female and males accounted for 2.45% of the cases. Among females, 40-55 was the most prevalent age group. CONCLUSION: The incidence of breast cancer among women living in southern Iran showed an increasing trend from 2001 to 2018. However, the rate of increase exhibited a milder slope during the more recent years. Based on the higher prevalence of breast cancer in the 40-55 age group observed in the present study, it offers valuable insight into the potential reduction of the breast cancer screening age from 50 to 40 years for healthy Iranian women. However, before implementing such a policy change, it is crucial to conduct additional studies that specifically examine the cost-effectiveness, as well as the potential benefits and risks associated with this alteration.

The Effects of Resveratrol, Gallic Acid, and Piperine on the Expression of miR-17, miR-92b, miR-181a, miR-222, BAX, BCL-2, MCL-1, WT1, c-Kit, and CEBPA in Human Acute Myeloid Leukemia Cells and Their Roles in Apoptosis.

MicroRNAs (miRs) play a crucial role in the leukemogenesis and the prognosis of acute myeloid leukemia (AML). This study investigated the therapeutic effects of resveratrol, gallic acid, and piperine as natural anticancer agents on the HL-60 cell line and their roles in apoptosis. In this experimental study, quantitative analysis of miRs, including miR-17, miR-92b, miR-181a, and miR-222, were performed in 150 newly diagnosed patients with AML by real-time PCR assay. HL-60 cell viability as well as the expression of miRs, BAX, BCL-2, MCL-1, WT1, c-Kit, and CEBPA, were also assessed after transfection with the LNA-miRs and treatment with resveratrol, gallic acid, and piperine. The expression of miR-17 and miR-181a decreased significantly in LNA-anti-miRs. Although HL-60 cell viability decreased in LNA-anti-miR-222, miR-17, and miR-92b, blockade of miR-181a increased the cell viability. Besides, the cell viability increased merely in the piperine-treated group. Compared to untreated cells, miR-17 and miR-92b expression significantly increased in gallic acid- and resveratrol-treated cells. In HL-60 cells treated with resveratrol, gallic acid, and piperine, the expression of miR-181a was also increased significantly. The expression of BAX was also increased in resveratrol and piperine-treated groups. Compared to untreated cells, the expression of c-Kit increased significantly in the piperine-treated group; however, it decreased in the resveratrol-treated group. LNA-anti-miRs may be a promising agent for the treatment of AML. All three compounds used in this study showed anticancer effects, which can exert the desired outcome in patients with AML.

Higher Peripheral Blood IFN-γ-/IL-4+ Th2 Lymphocytes Are Associated with Lower Rate of Relapse in Patients with Lymphoma.

BACKGROUND: The role of T-helper lymphocytes especially T helper 2 (Th2) subsets in lymphoid malignancies is debatable and unknown. METHODS: Herein, we evaluated the polarization of the IFN-γ+/IL-4- Th1 and IFN-γ-/IL-4+ Th2 lymphocytes in 95 lymphoma patients including 47 classical Hodgkin's lymphoma (cHL) and 48 diffuse large B cell lymphoma patients (DLBCL) at different disease phases and its correlation with the clinical outcomes of patients using flow cytometry method. RESULTS: The proportion of IFN-γ+/IL-4- Th1 lymphocytes was significantly higher in cHL patients at remission compared to the newly diagnosed ones. Both cHL and DLBCL patients at remission phase had significantly more IFN-γ-/IL-4+ Th2 lymphocytes than those patients at relapse/refractory phase as well as newly diagnosed ones. Despite having higher frequency of IFN-γ+/IL-4- Th1 lymphocytes, the mean fluorescent intensity (MFI) of IFN-γ was lower in relapsed cHL patients, in those with high-risk IPI score, performance status (PS) ≥2 and B symptom-positive groups compared to their corresponding counterparts in newly diagnosed patients. CONCLUSION: Taken together, higher peripheral blood IFN-γ-/IL-4+ Th2 lymphocytes might be associated with a favorable prognosis like lower rate of relapse in lymphoma patients.

Pain, Fatigue, Nausea, and Vomiting as the Predictors of Anxiety in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Prospective Cohort Study.

The primary outcome was to assess the correlation between anxiety and pain, fatigue, nausea, and vomiting. The secondary outcome was to determine the predictive roles of pain, fatigue, nausea, and vomiting in anxiety among patients undergoing Hematopoietic Stem Cell Transplantation (HSCT). The present prospective cohort study was conducted on 200 patients treated by HSCT referred to the centers affiliated to Shiraz University of Medical Sciences. The data were collected using Spielberger Anxiety Questionnaire, Numerical Pain Scale, Brief Fatigue Inventory, and Rhodes Nausea and Vomiting Index. The data were analyzed using Spearman's test and multiple regression analysis. The means of state anxiety, trait anxiety, pain, fatigue, and nausea, vomiting, and retching were 41.67 (SD = 9.71), 43.78 (SD = 9.00), 3.79 (SD = 2.79), 4.23 (SD = 2.48), and 6.31 (SD = 7.53), respectively. The results showed that the participants with higher pain and fatigue scores had higher anxiety levels. Those with more nausea and vomiting had higher anxiety levels, as well. This indicated that fatigue, pain, severity and frequency of nausea, and type of HSCT were the predictors of trait anxiety. The results also showed the predictor role of pain, fatigue, and type of HSCT in state anxiety. The findings revealed a correlation between anxiety and pain, fatigue, nausea, and vomiting among the HSCT patients. The results also showed fatigue and pain as the predictors of anxiety among these patients. Yet, future studies are recommended to determine the other factors contributing to anxiety amongst HSCT patients.

MicroRNAs: Regulatory Biomarkers in Acute Myeloid Leukemia and Graft Versus Host Disease.

BACKGROUND: MicroRNAs are a group of small non-coding RNAs with about 19 - 22 nucleotides and have a crucial role in different biologic processes such as cell proliferation, differentiation, and cell death at the post-transcriptional level. Disruption in these molecules can play an important role in tumorigenesis, and they can act as oncogenes or tumor suppressors. Acute myeloid leukemia (AML) is a hematologic malignancy with abnormal proliferation and differentiation of immature myeloid cells. MicroRNAs can be considered as biomarkers for diagnosis, prognosis, and treatment in AML patients. One of the treatments in these patients is hematopoietic stem cell transplantation (HSCT), and acute graft versus host disease (aGVHD) is the most common complication of HSCT in these patients. Patients with aGVHD appear with different clinical symptoms. Some microRNAs can predict the risk of aGVHD in these patients. METHODS: The resources of this study are from different sites and journals such as ncbi.nlm.nih.gov/pubmed, scopus.com, Blood Journal, British Journal of Haematology, etc. Results: The expression of various microRNAs is different in AML patients. Also, these differences can be observed in patients with aGVHD. CONCLUSIONS: Identification of microRNAs can be useful in the diagnosis and prognosis of AML and aGVHD in these patients. In this review, we discuss the role of microRNAs in the pathogenesis of AML and aGVHD in patients who have undergone HSCT.

Cytokine Levels in Patients with ß-Thalassemia Major and Healthy Individuals: a Systematic Review and Meta-Analysis.

BACKGROUND: Cytokine levels in patients with ß-thalassemia major (ß-TM) have been assessed in several studies. Accordingly, a wide variety of immune disturbances has been shown in patients with thalassemia. Recurrent transfusions cause iron overload, which induces an increase in the production of cytokines. However, no systematic approach or meta-analysis has been done to provide a clear feature of cytokine levels in ß-TM. The present meta-analysis aimed to summarize the existing evidence regarding different levels of cytokines in patients with Β-TM compared to healthy controls. METHODS: This study was performed according to the PRISMA checklist. A systematic search was done in Web of Science (ISI), Scopus, and PubMed databases. The quality of the included studies was assessed based on the New-castle-Ottawa Scale. Meta-analysis was run via STATA 13 software. The standardized mean difference was considered the effect size for comparing the continuous variables. RESULTS: This meta-analysis included 16 studies conducted on 805 ß-TM patients and 624 healthy individuals (with the mean age of 16.10 ± 4.33 and 16.22 ± 3.78, respectively). The results showed significantly higher levels of Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and IL-10 in patients with ß-TM compared to the healthy controls. CONCLUSION: The results indicated that the levels of both inflammatory and anti-inflammatory cytokines were higher in patients with ß-TM compared to the healthy population, which could be associated with higher levels of oxidative markers in these patients. Further studies are suggested to evaluate the difference in cytokine levels among different types of thalassemia.

Investigating the impact of modified mindfulness-based stress reduction (MBSR) program on occupational burnout and other mental health status among nonmedical staff in a hospital: a randomized controlled trial.

OBJECTIVE: Burnout is a prolonged psychological response to a longstanding interpersonal stressor at work. It can progress to other mental illnesses, such as anxiety and depression. In today's society, burnout has become widespread, and it is currently a serious challenge in health systems. This study intended to investigate the impact of mindfulness training on burnout and depression, anxiety, and stress of nonmedical staff in a hospital in Shiraz-Iran. METHOD: Fifty nonmedical staff in a Shiraz-Iran hospital were enrolled in this two groups' randomized controlled trial. The intervention group was trained by a modified mindfulness-based stress reduction (MBSR) program, and the control group received no intervention. The outcome was assessed by the Copenhagen burnout inventory (CBI) and DASS-21 questionnaire on three occasions including before T0, immediately after T1, and 3 months after the intervention T2. RESULTS: Comparing the score changes between intervention and control groups showed that the reduction of work­distaste­related burnout, client­related burnout, anxiety, and stress scores in the intervention group was significantly more than in the control group in the time interval from T0 to T1. The scores in the intervention group in three subscales of CBI, including work­characteristic­related burnout, work­distaste­related burnout, and client­related burnout, decreased significantly immediately after the training (T1) compared to before (T0). Also, the scores did not change significantly after 3 months following training. CONCLUSIONS: Mindfulness training can be used as an effective way to improve occupational burnout, anxiety, and stress in occupations other than health professionals. Its effect is stable for at least a few months. It is recommended that future studies focus on investigating the feasible way to integrate this training into the working environment. Forthcoming studies should also determine whether the impact of this intervention will last longer and find possible ways to extend its influence.

Oncogenic and tumor suppressor genes expression in myeloproliferative neoplasms: The hidden side of a complex pathology.

BACKGROUND: The present study aimed to explore the changes in the expressions of six tumor-related genes in myeloproliferative neoplasms (MPNs). The study population included 130 patients with MPNs (52 with chronic myeloid leukemia (CML), 49 with essential thrombocythemia (ET), 20 with polycythemia vera (PV), and 9 with primary myelofibrosis (PMF)) and 51 healthy individuals. METHODS: The expression profiling of six genes (ADAMTS18, CMTM5, CDKN2B, DCC, FHIT, and WNT5B) in the peripheral blood granulocyte cells was explored by real-time quantitative reverse transcription polymerase chain reaction. RESULTS: The patients with MPNs showed significant downregulation of CMTM5 (EFC = 0.66) and DCC (EFC = 0.65) genes in contrast to a non-significant upregulation of ADAMTS18, CDKN2B, FHIT, and WNT5B genes. Downregulation of DCC was consistent in all subtypes of MPN (EFC range: 0.591-0.860). However, CMTM5 had a 1.22-fold upregulation in PMF in contrast to downregulation in other MPN subtypes (EFC range: 0.599-0.775). The results revealed a significant downregulation in CMTM5 and DCC at below 60-years of age. Furthermore, female patients showed a clear-cut downregulation in both CMTM5 and DCC (EFC DCC: 0.436 and CMTM5: 0.570), while male patients presented a less prominent downregulation with a borderline p-value only in DCC (EFC: 0.69; p = 0.05). CONCLUSIONS: Chronic myeloid leukemia cases showed a significant upregulation of WNT5B, as a known oncogenesis gene. Two tumor suppressor genes, namely DCC and CMTM5, were downregulated in the patients with MPNs, especially in females and patients below 60 years of age.

The impact of selenium on regulatory T cell frequency and immune checkpoint receptor expression in patients with diffuse large B cell lymphoma (DLBCL).

For many decades, selenium (Se) has been known as a potential anti-cancer agent that can also improve the function of immune cells in a variety of solid tumors. However, there is no report on the role of Se on CD4+ T cell subsets like CD4+CD25+FOXP3+ regulatory T cells (Tregs) in lymphoma patients. In this randomized clinical trial, we investigated the effect of 3-month Se consumption on the frequency of CD4+CD25+FOXP3+ Tregs and the expression of immune checkpoint receptors in thirty-two non-Hodgkin lymphoma (NHL) patients (16 patients with Se (Se+) and 16 without Se (Se-) consumption) with diffuse large B-cell lymphoma (DLBCL) subtype at stable remission. The change in the frequency of Tregs and expression of immune checkpoint receptors including CTLA-4, LAG-3, TIM-3, and PD-L1 genes were evaluated after 3 months in both groups using flow cytometry and SYBR Green Real-time PCR method, respectively. The results showed that the frequency of CD4+CD25+FOXP3+ Tregs and expression of immune checkpoint receptors did not significantly change after 3-month Se consumption in DLBCL patients. However, alteration in the frequency of CD4+CD25-FOXP3+ Treg subsets was positively correlated with change in CTLA-4, LAG-3, and TIM-3 expression in the Se+ group. Three-month Se supplementation did not prevent relapse in Se+ group. Taken together, Se supplementation alone did not affect the frequency of CD4+CD25+FOXP3+ Tregs, expression of checkpoint receptors, and prevention of relapse in DLBCL patients at stable remission phase but might influence the functional properties of other Treg subsets like CD4+CD25-FOXP3+ Tregs.

The Prevalence of Hypothyroidism among Patients With ß-Thalassemia: A Systematic Review and Meta-Analysis of Cross-Sectional Studies.

As a cause of chronic blood transfusions, iron overload is an important issue in ß-thalassemia (ß-thal) patients that leads to multiple organ dysfunctions. This is an updated meta-analysis conducted to summarize the existing evidence of the prevalence of hypothyroidism (HT) among patients with transfusion-dependent (TDT) and non transfusion-dependent ß-thal (NTDT) and for the first time we meta-analyzed the relationship between ferritin level and HT. This systematic review and meta-analysis were done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. We searched databases including Web of Science (ISI), Scopus, PubMed, Embase, and Scholar. The quality of the included studies was assessed based on the Newcastle-Ottawa scale (NOS) checklist. Meta-analysis was done using Stata statistical software. The pooled prevalence of total HT, subclinical HT, and overt HT among ß-thal patients was 13.25 [95% confidence interval (95% CI): 10.29-16.21; 11.84, 95% CI: 8.43-15.25 and 12.46, 95% CI: 1.05-23.87], respectively. The prevalence of total HT was 16.22% (95% CI: 12.36-20.08) in TDT and 7.22% (95% CI: 3.66-10.78) in NTDT patients. Serum ferritin (SF) levels were significantly lower in euthyroid compared to hypothyroid patients [standard mean difference (SMD) -2.15 (95% CI: -3.08, -1.21, p value <0.001]. The prevalence of HT was higher in TDT compared to NTDT patients. Moreover, our results showed a significant association of high serum ferritin (SF) levels with hypothyroidism in ß-thal patients. Both of these findings highlight the importance of prevention measures and timely diagnosis and management of iron overload in ß-thal patients.

Aberrant peripheral blood CD4+ CD25+ FOXP3+ regulatory T cells/T helper-17 number is associated with the outcome of patients with lymphoma.

Little is known about the clinical significance of the peripheral blood CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) and T helper-17 (Th17) cells in lymphoma patients. In this study, the prognostic and clinical significance of peripheral blood Tregs and Th17 cells were evaluated in lymphoma patients during different phases. The frequency of Tregs and Th17 lymphocytes was measured by flow cytometry method in 47 classical Hodgkin's lymphoma (cHL) and 48 diffuse large B cell lymphoma (DLBCL) patients. Our results showed that the frequency of Tregs and absolute Treg count was significantly reduced in relapsed patients compared to patients at the remission phase, as well as with newly diagnosed untreated patients in both groups. Patients who reached complete remission had elevated frequency of CD4+ FOXP3+ lymphocytes, Tregs, absolute Treg count, Treg/CD4 and Treg/Th17 ratio in the cHL group and CD4+ CD25+ cells in DLBCL group. The frequency of Tregs, absolute Treg count and Treg/Th17 ratio in cHL patients and CD4+ FOXP3+ and CD4+ CD25+ cells in DLBCL patients positively associated with survival rate. Moreover, the percentage of Tregs and absolute Treg count positively correlated with white blood cell, platelet count and ESR level in cHL patients and with white blood cell count in DLBCL patients. The initial number of Tregs/Th17 cells and also the Treg/Th17 ratio was not associated with changes in disease-free survival (DFS) in both groups. Therefore, higher frequency of peripheral blood Tregs and Treg/Th17 ratio might be associated with a favorable outcome in lymphoma patients, better response to chemotherapy and lower rate of relapse.

Association of killer-cell immunoglobulin-like receptor genes with acute myelogenous leukaemia.

Killer-cell immunoglobulin-like receptors (KIRs) are important because of their key roles in NK cell development and function. Some KIR genes have been associated with the incidence of haematological malignancies. This study was designed to determine whether the inheritance of specific KIR genes is associated with susceptibility to acute myelogenous leukaemia (AML) in Persians living in south-western Iran. KIR genes and KIR2DS4 variants were typed by polymerase chain reaction-sequence-specific primer (PCR-SSP) in 167 patients with AML and 169 healthy controls. Our results showed 10% of patients-mostly females-were classified as M3. Flt3 mutations were detected in 26% of patients, most of whom had internal tandem duplication (ITD). The frequency of activating KIRs (aKIRs)-mainly KIR3DS1-was higher in patients, whereas inhibitory KIRs (iKIRs)-particularly KIR3DL1 and KIR2DL1-were more common among controls. The incidence of the KIR2DS4fl allele was higher among patients with non-M3 AML than controls. We also found a higher frequency of 4 or more iKIR genes in the controls and a higher frequency of 4 or more aKIR genes in the patients. Individuals with more iKIR than aKIR belonged predominantly to the control group. Individuals with the telomeric AA genotype who had inherited the KIR2DS4fl allele were more frequent in the patient group. According to our results, increased frequency of aKIRs in patients with AML may lead to the hyperactivation of NK cells against malignant cells with reduced or lack of HLA class I molecules followed by NK cell exhaustion which allow malignant cells to progress.

Ocular findings in patients with transfusion-dependent ß-thalassemia in southern Iran.

BACKGROUND: Ocular involvement may occur via several mechanisms in patients with transfusion-dependent ß-thalassemia (TDT) mainly chronic anemia, iron overload and iron chelator toxicity. We aimed to evaluate the frequency of abnormal ocular findings and their relationship with hematologic parameters in TDT patients. METHODS: In this cross-sectional study from January 2018 to January 2019, a total of 79 patients with TDT over the age of 18 who were on iron-chelation therapy (ICT) were consecutively investigated. All patients were registered at the Thalassemia Comprehensive Center affiliated with Shiraz University of Medical Sciences, Shiraz, Southern Iran. Complete ophthalmic examination was performed by an expert ophthalmologist. Clinical and hematologic parameters were collected from the patients´ medical records. RESULTS: The mean age ± standard deviation (SD) of the patients was 28.4 ± 5.6 years (range: 18-43). Twenty-four patients (30.4%) were male and 29 (36.7%) were splenectomized. The mean ± SD of the best-corrected visual acuity (VA) was 0.960 ± 0.086 decimal, (range: 0.6-1), 0.016 ± 0.046 logMar, (range: 0-0.2). The frequency of patients with VA > 0.1 logMar was 3 (3.8%). The mean intraocular pressure (IOP) was 14.88 ± 3.34 (6-25) mmHg. Fundus abnormalities were observed in 8 patients (10.1%), consisting of increased cup-disk ratio (3.8%), vessel tortuosity (2.5%), retinal pigment epithelium degeneration (2.5%), myelinated nerve fiber layer (1.3%), and internal limiting membrane wrinkling (1.3%). No significant association was observed between fundus abnormalities, VA, or IOP with hematologic parameters (P > 0.05). TDT patients with diabetes mellitus had significantly higher IOP (P = 0.010) but similar frequency of fundus abnormalities with non-diabetic patients (P > 0.05). CONCLUSIONS: The frequency of ocular abnormalities in our patients was lower than the previous reports. The frequency of fundus abnormalities were similar in diabetic and non-diabetic thalassemia patients indicating close monitoring and proper management of the disease and comorbidities in these patients.

Relationship of the Interaction Between Two Quantitative Trait Loci with γ-Globin Expression in ß-Thalassemia Intermedia Patients.

Globin switching is a significant factor on blood hemoglobin (Hb) level but its molecular mechanisms have not yet been identified, however, several quantitative trait loci (QTL) and polymorphisms involved regions on chromosomes 2p, 6q, 8q and X account for variation in the γ-globin expression level. We studied the effect of interaction between a region on intron six of the TOX gene, chromosome 8q (chr8q) and XmnI locus on the γ-globin promoter, chr11p on γ-globin expression in 150 ß-thalassemia intermedia (ß-TI) patients, evaluated by statistical interaction analysis. Our results showed a significant interaction between one QTL on intron six of the TOX gene (rs9693712) and XmnI locus that effect γ-globin expression. Interchromosomal interaction mediates through transcriptional machanisms to preserve true genome architectural features, chromosomes localization and DNA bending. This interaction can be a part of the unknown molecular mechanism of globin switching and regulation of gene expression.

Leukemia microvesicles affect healthy hematopoietic stem cells.

Microvesicles are released by different cell types and shuttle mRNAs and microRNAs which have the possibility to transfer genetic information to a target cell and alter its function. Acute myeloid leukemia is a malignant disorder, and leukemic cells occupy all the bone marrow microenvironment. In this study, we investigate the effect of leukemia microvesicles on healthy umbilical cord blood hematopoietic stem cells to find evidence of cell information transferring. Leukemia microvesicles were isolated from acute myeloid leukemia patients and were co-incubated with healthy hematopoietic stem cells. After 7 days, cell count, hematopoietic stem cell-specific cluster of differentiation (CD) markers, colony-forming unit assay, and some microRNA gene expressions were assessed. Data showed a higher number of hematopoietic stem cells after being treated with leukemia microvesicles compared with control (treated with no microvesicles) and normal (treated with normal microvesicles) groups. Also, increased levels of microRNA-21 and microRNA-29a genes were observed in this group, while colony-forming ability was still maintained and high ranges of CD34+, CD34+CD38-, CD90+, and CD117+ phenotypes were observed as stemness signs. Our results suggest that leukemia microvesicles are able to induce some effects on healthy hematopoietic stem cells such as promoting cell survival and some microRNAs deregulation, while stemness is maintained.

Association of IL-17 gene polymorphisms and serum level with graft versus host disease after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Cytokines are important factors determining the outcome of transplantation. Host ability in cytokine production may be affected by cytokine genes polymorphisms. The aim of the present study was to investigate the effect of IL-17 gene polymorphisms on outcome of Hematopoietic stem cell transplantation. MATERIALS AND METHODS: A total of 60 bone marrow recipients were included in this study. Twenty-five recipients (41.66%) underwent a GVHD. IL-17 gene polymorphisms were evaluated by PCR-RFLP method and the serum levels were also checked by ELISA. RESULTS: No significant differences in distribution of the IL-17(A/G) (rs3819025) genotypes and alleles were observed between two groups. But, IL-17 (A/G, -197) GG genotype was found to be significantly higher in GVHD group compared to those of non-GVHD group (P = 0.04). Interestingly, after stratification of patients according severity of GVHD, IL-17 (rs3819025) G allele was remained significantly higher in GVHD grade (0-I) group compared to those of grade (II-IV) group (P = 0.05). In addition, after categorization of patients according to their sex, IL-17-197 GG genotype showed a significant association with non-GVHD in male patients (P = 0.05). IL-17 serum levels did not show any significant difference between GVHD and non GVHD groups. CONCLUSION: Results indicated that IL-17197 GG genotype, G allele of (rs3819025) and its serum level have predictive values for severity of GVHD. Also, IL-17-197 GG genotype is a sex dependent genetic risk factor for development of GVHD, but this subject need to be studied in different population.

Polymorphism of costimulatory molecules (CTLA4, ICOS, PD.1 and CD28) and allogeneic hematopoietic stem cell transplantation in Iranian patients.

Costimulatory molecules are important factors determining the outcome of bone marrow transplant. Because the host ability in costimulatory molecule function may be affected by gene polymorphisms, the aim of the present study was to investigate the effect of CTLA4, ICOS, PD.1 and CD28 gene polymorphisms in outcome of bone marrow transplant patients. A total of 72 recipients were included in this study. CTLA4 (-1722, -1661, -318, +49), ICOS (+1720), CD28 (+17) and PD.1 (PD.1.3, PD.1.9) gene polymorphisms were evaluated by PCR-RFLP. The results showed that no differences in the distribution of all mentioned costimulatory molecules genotypes and alleles were observed in the Graft Versus Host Disease (GVHD) group compared to the non-GVHD group. After gender classification, there is a significant association between GA genotype (CTLA4-1661) in male group with GVHD than without GVHD (p=0.03). Also, in this study we found significant associations between CC genotype and C allele of PD.1.9, and TT genotype and T allele of CD28 that had more frequency in grades 2-4 (p=0.04. p=0.02, p=0.01, p=0.003, respectively). Results indicate that the CC genotype and C allele of PD.1.9 and TT genotype and the T allele of CD28 are genetic risk factors for development of a severe grade of GVHD. This subject needs to be studied in different population.

Epidemiology of hemoglobinopathies and thalassemias in individuals referred to the haematology research centre, Shiraz University of Medical Sciences, Shiraz, Iran from 2006 to 2011.

Hemoglobinopathies and thalassemias are the most frequent genetic hereditary disorders with an increasing global health burden, especially in low- and middle-income countries. We aimed to determine the epidemiologic pattern of hemoglobinopathies and thalassemias in individuals referred to the Haematology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran, which is the most important referral center in Southern Iran during 2006 to 2011. The most frequent abnormality was ß-thalassemia (ß-thal) minor (24.0%), followed by α-thalassemia (α-thal) trait (10.0%), hemoglobin (Hb) S trait (4.0%) and Hb D-Punjab trait (4.0%). Because this center is a referral center, we detected a higher prevalence compared to the normal population; however, these data could help policymakers and health service providers to better programming for prevention of births affected with Hb disorders.