Effect of the uncoupling protein-2 (UCP-2) and nuclear receptor subfamily 3 group C member 1 (NR3C1) genes on treatment efficacy and survival in patients with multiple myeloma: a single-center study.

OBJECTIVE: Studies on the genetic background of patients with multiple myeloma (MM) have been increasing; two important factors considered in such works are uncoupling protein-2 (UCP-2) and nuclear receptor subfamily 3 group C member 1 (NR3C1). We aim to reveal the association of MM with NR3C1 and UCP-2 gene polymorphisms. In this prospective study, 200 patients diagnosed between January 2009 and 2018 and 200 healthy individuals were included. For patients who had undergone autologous stem cell transplantation and control subjects, we statistically compared the CC, GC, and GG genotypes and the C and G alleles of the NR3C1 gene, as well as the AA, AG, and GG genotypes and the A and G alleles of the UCP-2 gene. RESULTS: While the AA genotype was significantly more common in the MM group (p = 0.001), the GG genotype was significantly more common in the control group (p = 0.016). Overall survival was found to be significantly shorter in patients with the UCP-2 GG genotype (p = 0.034). It was also found that having the GG genotype of the UCP-2 gene was a 2.48-fold risk factor for mortality. The fact that overall survival is significantly shorter in MM patients with the UCP-2 GG genotype and its definition as a risk factor for mortality have been put forward for the first time in the literature.

Incidence and risk factors for hepatic sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: A retrospective multicenter study of Turkish hematology research and education group (ThREG).

Hepatic sinusoidal obstruction syndrome (HSOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the incidence, risk factors, treatment and survival for HSOS after allo-HSCT in Turkey. We also reported our experience of defibrotide (DF) for HSOS prophylaxis in high-risk (HR) patients. Across Turkey, 1153 patients from 10 centers were enrolled in the study. We evaluated the medical records of patients who were treated with allo-SCT between January 2012 and December 2015. The study included 1153 patients (687 males/466 females) with median age of 38 (15-71) years. The incidence of HSOS was 7.5 % (n = 86). The incidences of HSOS in the HR/DF+, HR/DF- and standard risk (SR) group were 8%, 66.7 % and 6.2 %, respectively. The rate of HSOS development was not statistically different between HR/DF + and SR group (p = 0.237). HSOS prophylaxis (defibrotide) was significantly decreased HSOS-related mortality (p = 0.004). The incidence of HSOS was found similar to literature in this large Turkish cohort. Defibrotide prophylaxis appears to be associated with low incidence of HSOS development and reduced HSOS-related mortality. Although these results are promising, future studies are needed to support the efficacy of defibrotide prophylaxis in patients with risk of HSOS.

The Associations of IL-6, IFN-γ, TNF-α, IL-10, and TGF-ß1 Functional Variants with Acute Myeloid Leukemia in Turkish Patients.

AIM: It has been suggested that cytokine dysregulation could be associated with pathogenesis, progression, and survival in acute myeloid leukemia (AML). The purpose of this study was to evaluate the relationship of functional single-nucleotide polymorphisms (SNPs) in cytokine gene and cytokine expression levels with AML. MATERIALS AND METHODS: Peripheral blood samples were collected from 42 patients with AML and 85 healthy individuals. Eight SNPs in five cytokine genes, including interleukin 6 (IL-6), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and transforming growth factor-ß 1 (TGF-ß1), were analyzed using the polymerase chain reaction sequence-specific primer method. RESULTS: We found that the frequencies of the TNF-α (-308) GG genotype and G allele were significantly higher in the patients with AML compared to the healthy control group (p = 0.020 and 0.014). The AML patients had significantly lower frequencies of the CC genotype and C allele of the IL-10 (-819 SNP), the G allele of the IL-10 (-1082 SNP), the CC genotype and C allele of the IL-10 (-592 SNP), and the codon 25 GC genotype of TGF-ß1, (p = 0.024, p = 0.012, p = 0.038, p = 0.024, p = 0.012, p = 0.028, respectively). However, no significant differences were found between AML and healthy control groups with respect to the distributions of genotypes in IL-6, IFN-γ, IL-10 (-1082), TGF-ß1 (codon 10), and haplotypes of IL-10, TGF-ß1 gene. CONCLUSION: Our results suggest that functional variants of the TNF-α, IL-10, and TGF-ß1 genes may have a significant association with the etiopathogenesis of AML. Further studies with larger groups and different ethnicities are needed to determine the impact of cytokine variants on the risk of developing AML.

Evaluation of patients diagnosed with fascioliasis: A six-year experience at a university hospital in Turkey.

INTRODUCTION: In this study, clinical, laboratory, radiological, and serological examinations of fascioliasis patients were analyzed, and data with a significant impact on differential diagnosis were evaluated. METHODOLOGY: Clinical, radiological, and laboratory findings and treatment responses of a total of 22 fascioliasis patients, treated between October 2009 and September 2014, were evaluated. Nineteen patients were diagnosed with fascioliasis at the invasive phase and three patients at the chronic phase. Patients were followed up for clinical, laboratory, and radiology findings for a period of three months to one year after treatment. RESULTS: The most frequent complaints in both groups were abdominal pain, and the most common physical examination finding was epigastric tenderness. In the performed examination, an eosinophil elevation in whole blood count was detected in 19 patients (100%) in the hepatic phase, and in 2 patients (66.6%) in the biliary phase. The results of the Fasciola hepatica indirect hemagglutination assay (IHA) test ordered in the diagnosis were positive in all patients. Treatment with 10 mg/kg/day triclabendazole for two consecutive days was effective. Live parasites were extracted from patients in the biliary phase with endoscopic retrograde cholangiopancreatography. In the follow-ups, remission in IHA titer and clinical and radiological improvement was achieved in all patients. CONCLUSIONS: If hypereosinophilia is detected by peripheral smear in patients who are admitted with complaints such as abdominal pain, weakness, nausea, myalgia, and weight loss, radiological evaluation and serological tests should be performed and fascioliasis should be considered in the differential diagnosis.

Q192R and L55M Polymorphisms of Paraoxonase 1 Gene in Chronic Myelogenous Leukemia and Chronic Lymphocytic Leukemia.

AIM: The aim of the present study was to investigate the association between Paraoxonase 1 (PON1) gene polymorphisms Q192R, and L55M in patients with Chronic Myelogenous Leukemia (CML) and Chronic Lymphocytic Leukemia (CLL) patients. MATERIALS AND METHODS: We analyzed samples from 60 patients with CML, 60 with CLL and 84 healthy controls. Polymerase Chain Reaction (PCR)--Restriction Fragment Length Polymorphism (RLFP) was performed and samples were run in agarose gel. RESULTS: We found statistically significant results showing an increase in both the RR genotype (p=0.044) and the R allele (p=0.011) for PON1 Q192R, and an increase in the MM genotype (p=0.007) and a decrease in the LL genotype (p=0.004) and R allele (p=0.001) in PON1 L55M in patients with CLL. CONCLUSION: We concluded that both the Q192R gene polymorphism with an increase in the genotype R allele, and the M/L55 with an increase in the MM genotype play a role in CLL susceptibility, and a decrease in the LL genotype can act against disease in the Turkish population.

Prognostic importance of single-nucleotide polymorphisms in IL-6, IL-10, TGF-ß1, IFN-γ, and TNF-α genes in chronic phase chronic myeloid leukemia.

The aim of this study was to explore the association between polymorphisms of five cytokine genes and clinical parameters in patients with Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) treated with imatinib. We analyzed five cytokine genes (interleukin [IL]-6, IL-10, gamma interferon [IFN-γ], transforming growth factor beta-1 [TGF-ß1], and tumor necrosis factor-alpha [TNF-α]) in 60 cases with Ph+ CML and 74 healthy controls. Cytokine genotyping was performed by the polymerase chain reaction-sequence-specific primer. All data were analyzed using the de Finetti program and SPSS version 14.0 for Windows. No significant differences were detected between the CML group and healthy controls with respect to the distributions and numbers of genotypes and alleles in TNF-α, TGF-ß1, IL-10, and IFN-γ. However, the GG genotype associated with high expression in IL-6 was found to be significantly more frequent in CML as compared to controls (p=0.010). The median follow-up time was 49.3 months (range 6.1-168.4) and the median duration of imatinib treatment was 39.5 months (range 5.2-103.4) for these patients. On multivariateanalysis, only IL-10 GCC/GCC highly produced haplotypes were significantly associated with a shorter event-free survival. The relationship between cytokine genotypes/haplotypes and clinical parameters in CML has not been investigated before. Our results suggest that IL-10 may be a useful marker for CML prognosis and theGG genotype of the IL-6 gene may be associated with susceptibility.

Gene polymorphisms and febrile neutropenia in acute leukemia--no association with IL-4, CCR-5, IL-1RA, but the MBL-2, ACE, and TLR-4 are associated with the disease in Turkish patients: a preliminary study.

AIMS: The aim of this study was to investigate the mannose-binding lectin 2 (MBL-2), interleukin (IL)-4, Toll-like receptor 4 (TLR-4), angiotensin converting enzyme (ACE), chemokine receptor 5 (CCR-5), and IL-1 receptor antagonist (RA) gene polymorphisms (GPs) in acute leukemias (ALs) and to evaluate their roles in febrile neutropenia (FN) resulting from chemotherapy. METHODS: The study included 60 AL patients hospitalized between the period of July 2001 and August 2006. Polymorphisms for the genes ACE(I/D), CCR-5, IL-1RA, MBL-2, TLR-4, and IL-4 were typed by polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymerase. Genotype frequencies for these genes were compared in the patient and control groups. The relationships between the genotypes and the body distribution of infections, pathogens, the duration of neutropenia, and febrile episodes in AL patients were evaluated. RESULTS: No significant differences in either the genotype distribution or the allelic frequencies of TLR-4, IL-4, CCR-5, IL-1RN GPs were observed between patients and healthy controls. The AB/BB genotype (53.3%) in the MBL-2 gene was found to be significantly higher in the AL patients compared with control groups. There were correlations between the presence of MBL-2, TLR-4, and ACE polymorphisms and clinical parameters due to FN. Overall, bacteremia was more common in MBL BB and ACE DD. Gram-positive bacteremia was more common in ACE for ID versus DD genotype. Gram-negative bacteremia was more common for both the MBL-2 AB/BB genotype and TLR-4 AG genotype. Median durations of febrile episodes were significantly shorter in ACE DD and MBL AB/BB. CONCLUSION: Although TLR-4, ACE, and MBL-2 GPs have been extensively investigated in different clinical pictures, this is the first study to evaluate the role of these polymorphisms in the genetic etiopathogenesis of FN in patients with ALs. As a conclusion, TLR-4, ACE, and MBL-2 genes might play roles in the genetic etiopathogenesis of FN in patients with ALs.

Two cases with hypereosinophilic syndrome shown with real-time PCR and responding well to imatinib treatment.

The aim of this work was to report two cases of hypereosinophilic syndrome (HES). FIP1L1-PDGFRA fusion was assessed with two protocols at RNA level. The fusion transcript was found positive at the RNA level with both PCR methods in two cases. In this study, the efficiency of imatinib treatment and a dramatic response in two HES cases with multisystemic involvement showing the characteristics of a chronic myeloproliferative disease were presented. Both cases showed complete responses confirming that imatinib mesylate treatment could be successful even in patients with advanced HES having myeloproliferative disease.