Oxidative Status and Its Contribution to Extracellular Cytokine Secretion in Children with Acute Lymphoblastic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4471-4471
Author(s):  
Katarzyna Drabko ◽  
Agnieszka Bojarska-Junak ◽  
Jerzy R. Kowalczyk

Abstract Recent data suggest that oxidative-antioxidative imbalance may influence cytokine secretion in children with acute lymphoblastic leukemia (ALL). Plasma cytokines concentrations are reported to have an effect on clinical course of the patients with lymphoid malignancies. The aim of the study was analysis of oxidative status (Malonylodialdehyde, MDA) and antioxidant defense (Superoxide dismutase, SOD; glutathione peroxidase, GPX; total antioxidant status, TAS and vitamin E) in peripheral blood and evaluation of plasma concentration of IL-2, IL-4, IL-10 and TNF-alpha in children with acute lymphoblastic leukemia. Material and methods: Study group consisted of 23 newly diagnosed ALL children, including 13 boys and 10 girls, with median age 5 years (range, 0.5–16). Control group consisted of 21 healthy children (11 boys and 7 girls) with median age 7 years (range, 2–17). TAS, SOD, GPX status were estimated using commercially available Randox Laboratories Ltd kits. Vitamin E and MDA plasma concentrations were measured spectrofluorimetrically. Cytokine concentrations were measured by quantitative immunoassay tests: IL-2 and IL-4 plasma levels were assessed using Bender MedSystems test (Vienna, Austria), IL-10 and TNF-alpha by R&D system tests. All assays were performed twice: on diagnosis and 6 weeks thereafter. Results: GPX activity in study group was significantly higher before and during treatment than in control subjects (1.5-fold, p=0.02 and 2-fold, p=0.0007, respectively). MDA concentrations were higher in ALL group before treatment (1.4-fold, p=0.0001) and 6 weeks thereafter (1.2 fold, p=0.01) than in control group. SOD activity, TAS and vitamin E concentrations did not differ between the groups. IL-10 level was found to be significantly increased on ALL diagnosis, but not during therapy, when compared to control group (2-fold, p=0.02). TNF-alpha level was higher in patients before treatment then during treatment (3-fold, p=0.02) and as compare to the controls (2,5-fold, ns). IL-2 and IL-4 plasma concentrations were comparable in all groups in both time points. There was a correlation in children with ALL after 6 weeks therapy between MDA and IL-10 concentrations (r=0.59, p<0,05) as well as MDA and TNF-alpha concentrations (r=0,58, p<0,05). In control group MDA was correlated with IL-10(r=0.59, p<0.05). Median follow-up of the study group is 23 months, and at that time relapses occurred in 3 out of 23 patients. 2-fold decrease in median GPX were observed in patients, who relapsed afterward,. Median IL-10 plasma concentrations in children, who subsequently relapsed were 4-fold higher at diagnosis and 8-fold higher after 6 weeks of therapy then in patients who are still in remission (despite of achieving complete remission by all study group at 6th week of treatment). Conclusions: Oxidation process in plasma of children with ALL is significantly increased on diagnosis. Pro-oxidative status may contribute to IL-10 and TNF secretion and affect efficacy of treatment.

2021 ◽  
Author(s):  
Runhong Yu ◽  
Shiwei Yang ◽  
Yufeng Liu ◽  
Zunmin Zhu

Abstract Purpose: Study was by intention to screen serum autoantibodies that may contribute to the early detection of B-cell acute lymphoblastic leukemia (B-ALL) in children.Patients and methods: The total protein from three pooled B-ALL cell lines(NALM-6, REH and BALL-1 cells) was separated using two-dimensional gel electrophoresis(2-DE), which was followed by Western blot by mixed serum from B-ALL patients (n=20) or healthy children(n=20). We obtained and analyzed the images of 2-D gel and Western blot by PDQuest software,and then identify the spots of immune responses in B-ALL samples compared with those in control samples.The proteins from spots were identified using mass spectrometry (MS). The autoantibodies against α-enolase and voltage-dependent anion-selective channel protein 1(VDAC1) were further validated on the use of enzyme-linked immunosorbent assay(ELISA). The protein expression levels of the candidate antigens α-enolase and VDAC1 in B-ALL were thoroughly studied by immunohistochemical analysis.Results: Six protein dots were identified with MS as Aconitase,apoptosis-inducing factor(AIF),dihydrolipoamide dehydrogenase(DLD), α-enolase,medium-chain acyl-CoA dehydrogenase(MCAD) and VDAC 1.The frequencies of autoantibodies against α-enolase and VDAC1 in children with B-ALL were 27% and 23%, respectively, which were significantly higher than those in normal controls(4% and 0). Immunohistochemical analysis showed the expression of α-enolase and VDAC1 was positive in 95% and 85% of B-ALL patients, respectively, but negative expression levels were showed in the control group. Conclusion: This study incidates that α-enolase and VDAC1 may be the antigen associated with B-ALL .α-enolase and VDAC1 autoantibodies may develop into potential serological markers of B-ALL in children.Other proteins also need to be confirmed in a large number of serum samples.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3948-3948
Author(s):  
Oznur Yilmaz ◽  
Cetin Timur ◽  
Asim Yoruk ◽  
Muferet Erguven ◽  
Elif Aktekin ◽  
...  

Abstract In this study, we aimed to investigate epidemiologic factors in children with Acute Lymphoblastic leukemia (ALL). The parents of 105 children diagnosed and treated as ALL between the years 1997 –2007 in our Clinic of Pediatric Hematology-Oncology were questioned and results were compared with control group that consisted of 102 healthy children with similar age and gender. The mean age of the patients was 8.57 ± 3.95 years. The mean age at diagnosis was 5.87 ± 3.73 years. There was no significant difference between the groups in terms of type of delivery, birth weight, asphyxia at birth, resuscitation with high-concentration oxygen and ventilatory support (p&gt;0.05). There was also no significant difference between the groups in terms of duration of breast feeding. The rate of exposure to infections prior to diagnosis was higher in control group (p:0.003). Besides that, the rate of going to nursery was also significantly higher in control group (p:0.014). There was no difference between the groups in terms of X-ray exposure (p&gt;0.05). In conclusion over-protection from infectious agents in and delay in meeting with some specific agents seems to increase ALL risk. Infections in early infantile period can be protective against leukemia. There has to be more extended studies on this subject.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2623-2623
Author(s):  
Oscar Gonzalez-Ramella ◽  
Jimenez-Lopez Xochiquetzatl ◽  
Sergio Gallegos-Castorena ◽  
Pablo Ortiz-Lazareno ◽  
Jose Manuel Lerma-Diaz ◽  
...  

Abstract Introduction Acute lymphoblastic leukemia (ALL) is the most common cancer diagnostic in children, and it represents the second death cause in this population. Despite advances in the treatment of childhood ALL, there are small portion of patients whom still succumb to this disease. A reduced apoptosis in cells plays an important role in carcinogenesis. This phenomenon is an important component in the cytotoxicity induced by anticancer drugs. A currently challenge is the chemotherapy resistance of tumor cells, inhibiting the apoptosis induced by chemotherapy. Pentoxifylline, (PTX) has been studied for its role on increase of apoptosis on cancer cells by different pathways. Our group has reported its efficacy in vitro and ex vivo in increasing apoptosis induced by chemotherapy drugs such as adriamycin and cisplatin in fresh leukemic human cells, lymphoma murine models and cervical cancer cells. We conducted a phase 1 controlled randomized trial to evaluate the efficacy of adding PTX to the steroid window during the remission induction phase in new diagnosed children with ALL. Methods We included all children from both sexes from 9 months to 17 years old during October 2011 to December 2012. Patients were divided into 3 groups, the first one as a non-malignant control group (NL group) included children with a non-hematology disease in which bone marrow aspiration (BMA) was mandatory in order to reach the diagnosis. The second one, the ALL control group whom received prednisone (PRD group) for the steroid window at 40mg/m2/day PO from day -7 to day 0; and then the third one (PTX group), the study group which included children receiving the steroid phase with PRD as early described, plus PTX at 10mg/kg/day IV divided in 3 doses, at the same days as recommended in our treatment protocol (Total Therapy XV). For all 3 groups a BMA was performed at diagnosis, for PRD group as well as PTX group, a second BMA was also collected at day 0. Apoptosis was evaluated by means of Annexin V Apoptosis Detection Kit FITC/PI (eBioscience¨, San Diego, CA, USA) in 1×106 bone marrow mononuclear cells. We measured minimal residual disease (MRD) by flow cytometry at day 14 to demonstrate complete remission in leukemic patients. Statically analysis was performed by U Man Whitney. Results We enrolled 32 patients: 10 in NL group; 11 in PRD group; and 11 in PTX group. The median age of all groups was 6 years (range 9 months-17 years). In PRD group, patient 1 abandoned treatment after administration of day 0, nevertheless the second BMA sample was collected. Patient number 7 died at day 4 due to complications from tumor lysis syndrome. Consequently, in these patients we were not able to measure MRD and BM aspiration at day 14. Except one patient in PRD group, all achieved complete remission at day 14. We did not find any significant difference between NL group and PRD and PTX groups before intervention (U=32 p=0.7; U=28.5 p=0.48 respectively). There was no significant difference between treatment groups before intervention (U= 37 p=0.79). However, after treatment we found an important difference between PRD and PTX groups, we observed an increase in apoptosis in PTX group in comparison with PRD group (U=17.5 p=0.04). There were no adverse effects during treatment. Conclusions The present study is the first one that shows the efficacy of PTX in increasing apoptosis induced by PRD in new ALL diagnosed children, whom have not received any treatment yet. This might be helpful, not only in patients with relapse, but to increase the overall cure rate in ALL. Further studies are needed to prove this hypothesis. With this objective, our study group is already planning a second trial were PTX will be given during all remission induction phase. Experimental reports strongly suggest that PTX induces inhibition of the transcription factor NF-ĸB, by inhibiting survival gens and facilitating apoptosis. To prove it, we are currently processing these patients' samples to know their genetic expression. Disclosures: No relevant conflicts of interest to declare.


2014 ◽  
Vol 926-930 ◽  
pp. 1073-1076
Author(s):  
Zhong Hai Yuan ◽  
Yi Ju Hou ◽  
Chen Zhao ◽  
Yan Li

Abstract:Objective: To investigate whether any association exists between genetic polymorphism in CYP2B6 c.516G>T and individual susceptibility to acute lymphoblastic leukemia (ALL). Methods: Our study group consisted of 96 ALL patients(T-ALL 17 cases, B-ALL 79 cases) and 348 unrelated healthy newborn volunteers as a control group. Genomic DNA was extracted from peripheral blood and cord blood leukocytes. We genotyped CYP2B6 c.516G>T polymorphism by use of PCR with sequence-specific primers (PCR-SSP). The data were analyzed statistically using chi-square and logistic regression analyses. Results: The frequencies of GG genotype were 74.14%, 57.29%, 29.41% and 63.29%, and GT genotype were 23.85%, 37.50%, 64.71% and 31.65%, and TT genotype were 2.01%, 5.21%, 5.88% and 5.06% in control group, ALL, T-ALL, and B-ALL cases, respectively. Chi-square test showed a significant correlation between the CYP2B6 c.516G>T polymorphism GT genotype and ALL patients (OR=2.035, 95%CI=1.249-3.313, P=0.004); and T-ALL patients (OR=6.839, 95%CI=2.309-20.252, P=0.000); whereas and B-ALL patients (OR=1.554, 95%CI=0.906-2.667, P=0.108). Conclusions: This study revealed the CYP2B6 c.516GT genotype may be a risk factor to the development of ALL, especially T-ALL.


2018 ◽  
pp. 903-909 ◽  
Author(s):  
A. MASOPUSTOVÁ ◽  
P. JEHLIČKA ◽  
M. HUML ◽  
T. VOTAVA ◽  
L. TREFIL ◽  
...  

Acute lymphoblastic leukemia (ALL) and its treatment are associated with endothelial dysfunction (ED) and increased cardiovascular risk in adulthood. There are no data on ED in children after successful treatment of ALL. We aimed to assess new ED in these children using the plethysmographic reactive hyperemia index (RHI) and biomarkers that are known to be related to ED. In all, 22 children (mean 15.6 years), after successful treatment of ALL, and 18 healthy subjects were included in this prospective study. RHI, plasma concentrations of asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP) and E-selectin were measured in all children. RHI values were significantly lower in ALL patients when compared with healthy controls (p<0.05). hsCRP was significantly increased in ALL patients compared with the control group (p<0.001). E-selectin plasma levels were higher in ALL patients as compared to healthy controls (p=0.05). This is the first study that combines both plethysmographic and biochemical methods to assess ED in ALL survivors. Significantly decreased RHI with elevated plasma concentrations of biochemical markers imply a possible association with premature ED in ALL patients. The combined diagnostic approach seems to be a valuable tool for more accurate detection of ED and preventive cardiovascular management in these patients.


2021 ◽  
Vol 20 (1) ◽  
pp. 114-127
Author(s):  
N. N. Mitrakov ◽  
A. V. Shcherbukha ◽  
P. A. Shafran ◽  
K. A. Voronin ◽  
O. A. Laysheva

Movement disorders arising in pediatric patients with acute lymphoblastic leukemia (ALL) during treatment require a more differentiated approach to diagnosis and the choice of rehabilitation methods. The aim of this study was to investigate the conceptional structure of supine-to-stand (STS) transition patterns and to develop a method for the diagnosis of movement disorders and the assessment of the effectiveness of medical rehabilitation in children and adolescents with ALL. We carried out a prospective comparative non-randomized study. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. The study included 184 children who were assigned to three groups. Group 1 (study group) included patients with ALL treated at the Center (n = 48, the median age was 14.0 years). Group 2 (control group) included patients with various serious diseases (acute myeloid leukemia, primary immunodeficiency, CNS malignancies, bone tumors, etc.) who also underwent treatment at the Center (n = 69, the median age was 14.5 years). Group 3 (control group) included healthy children and adolescents (n = 67, the median age was 14.2 years). We analyzed the characteristics of video recordings of the supine-to-stand process in apparently healthy children (Group 3) and in the patients treated at the Center (Groups 1 and 2) and then performed comparative analysis. We managed to detect, document, and divide into phases the video-based criteria of invariant characteristics of the acyclic locomotor pattern of the STS movement (from a supine to standing position with both feet on the floor). We identified the STS movement phases and clinically significant variants of STS transition patterns which were easily detectable on the video recordings. The objectivity of the analysis of the video-based criteria of invariant characteristics of the STS movement was achieved by the registration of timing characteristics of the locomotion pattern phases on video recordings. By calculating the coefficients of variation for observations from different angles and inter-researcher variability, we detected the most representative phases of the STS movement pattern on video recordings. A quantitative analysis of the STS test performance revealed significant differences between healthy controls and children with oncological diseases. The clinical analysis of video recordings of the basic motor patterns (CLAVIR) contributes a substantial amount of objective data to the clinical assessment of the diagnostic supine-to-stand test results in children and adolescents treated for ALL. 


Author(s):  
Soheila Zareifar ◽  
Ali Alavi Shoushtari ◽  
Aida Abrari ◽  
Sezaneh Haghpanah

Background: Children with acute lymphoblastic leukemia (ALL) are prone to neurotoxicity and consequently neurocognitive function impairment mainly due to undergoing different treatment modalities. In the current investigation, neurocognitive function of children with ALL was compared to that of healthy children. Materials and Methods: In this cross-sectional study, 155 ALL and 155 age- matched healthy children in Shiraz, Southern Iran, were included and evaluated using Continuous Performance Test (CPT).  Results: Mean age of the patients was 9.9± 2.4 years. The number of wrong responses and duration of response did not lead to significant difference between healthy and affected children. In the age group less than 12 years old, the frequency of no-response was higher in the case group compared to control group both in boys and girls (P = 0.012, P = 0.006 respectively). In addition, in male patients younger than 12 years old, the number of correct responses was significantly less than that of  controls (P = 0.010). Patients underwent concurrent radiotherapy and chemotherapy needed significantly more time for responding compared to patients in whom chemotherapy were discontinued and were in remission (P=0.001). Conclusion: Based on the results, ALL children younger than 12 years old showed some defects in cognitive function. Moreover, it was more prominent in young boys compared to young girls. Regardless of the type of treatment regimens, early detection of neurocognitive disorders should be warranted in this high-risk population with more focus on boys and younger children. Psychological support and appropriate interventions can help improve cognitive function, reduce the disruption of education, and enhance the social and family relationships.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3950-3950
Author(s):  
Cetin Timur ◽  
Oznur Yilmaz ◽  
Asim Yoruk ◽  
Muferet Erguven ◽  
Timucin Imdadoglu ◽  
...  

Abstract In our study, we aimed to evaluate environmental and socio-economic conditions in children with Acute Lymphoblastic Leukemia (ALL) and to point at possible etiologic factors that can affect leukemia risk. The parents of 105 children diagnosed and treated as ALL between the years 1997 –2007 in our clinic of Pediatric Hematology-Oncology were questioned in terms of environmental and socio-economical factors and results were compared with control group that consisted of 102 healthy children with similar age and gender. Educational level and monthly income were similar between the groups. Occupational exposure of fathers to dust and chemicals were significantly higher in leukemia group (OR:2.00; %95 CI=1.41–3.50, p:0.015). Living near transformer stations (OR: 4.08; %95 CI= 1.3–12.76, p: 0.034) and high-voltage power lines (OR: 2.43; %95 CI= 1.05–5.63, p:0.01) is found to be associated with increased risk of leukemia in children. There was no significant difference in terms of living near base stations (p&gt;0.05). Exposure to industrial air pollution was significantly higher in leukemia group and was related to an elevated risk of ALL (OR: 26.77; %95 CI= 3.53–202.80, p:0.001). There was no significant difference in terms of exposure to insecticides and pesticides between the groups (p:&gt;0.05). In conclusion, leukemia is a disease with multi-factorial etiology that occurs as a result of interactions of genes and environment. The list of possible chemical, physical and biologic agents suspected to play a role in its etiology increase with developing technology and environmental pollution. However there are no sufficient data and more extended studies have to be carried out.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3937-3937
Author(s):  
Maria M Moschovi ◽  
Georgios G Trimis ◽  
Maria M Vounatsou ◽  
Katerina K Katsibardi ◽  
Alexandra A Margeli ◽  
...  

Abstract Disturbances in the production of adipocyte-derived hormones may represent a new link explaining the well-known relationship between obesity and increased prevalence of malignancies. Very few studies have evaluated adipokines concentration at diagnosis and during remission of a cancer. Purpose of our study was to investigate adipocytokines secretion, at diagnosis and during chemotherapy in children with acute lymphoblastic leukemia (ALL). Patients and Methods: Measurements were performed at diagnosis, after the induction-consolidation phase and at standard time points before each cycle in nine consecutive patients with ALL aged 2–7 years (median 4.3 yrs). All patients suffered from ≥5% BMI reduction in the 6 months before recruitment. BMI and leukemic burden were estimated at the same time points and correlated with adipocytokines levels. Nine healthy children matched for age and sex were used as controls. Results: At diagnosis, mean adiponectin levels were low (12.6±2.3 μg/ml vs. 18.2±2.4 μg/ml in controls, p&lt;0.0001) and mean leptin and resistin levels were high (27.4±4.2 ng/ml vs. 17.8 ± 3.4 ng/ml in controls, p&lt;0.001 and 5.2±1.2ng/ml vs. 3.2±1.1ng/ml in controls, p&lt;0.001, respectively). Compared to baseline values, mean adiponectin levels increased significantly to 16.6±2.9 μg/ml before the end of maintenance phase (p=0.024), while leptin and resistin fluctuated and stabilized at significantly lower levels (17.1±3.9 ng/ml, p=0.018 and 3.4±0.9 ng/ml, p=0.020, respectively), after the 8th cycle of chemotherapy. Mean adiponectin was still low, compared with controls, (p&lt;0.001), even after the 8th cycle. Delta (final-baseline) mean adiponectin was positively correlated with delta mean BMI-SD score of the patients (0.512, p=0.016), while delta mean leptin and resistin was negatively correlated with it (−0.626, p=0.009, and −0.527, p=0.013, respectively). However, when considering for lipids, LDH or leukemic burden, the positive association of adiponectin with BMI (0.087, p&gt;0.05) and the negative association of leptin and resistin with BMI do not persist (−0.098, p&gt;0.05 and −0.094, p&gt;0.05 respectively). Delta mean adiponectin was negatively correlated with leukemic burden (−0.439, p=0.019), while delta mean leptin and resistin was positively correlated with it (0.581, p=0.011 and 0.375, p=0.031, respectively). Delta mean adiponectin was negatively correlated with delta mean LDH (−0.315, p=0.041), delta mean triglycerides (−0.412, p=0.025) and positively correlated with delta mean HDL-C (0.306, p=0.042), while delta mean leptin and resistin was positively correlated with delta mean LDH (0.423, p=0.028, and 0.387, p=0.032, respectively), delta mean triglycerides (0.372, p=0.035, and 0.523, p=0.022, respectively) and negatively correlated with delta mean HDL-C (−0.467, p=0.020, and −0.356, p=0.034, respectively). Finally, delta mean BMI-SD was positively correlated with delta mean HDL-C (0.502, p=0.018) and negatively with delta triglycerides (−0.420, p=0.023) and delta LDH (−0.605, p&lt;0.010). Conclusion: Our results suggest that low serum adiponectin level and high leptin and resistin level are present in almost all patients with ALL at diagnosis. This is probably due to neuroendocrine imbalance and inflammation. The abnormalities are restored during remission. More studies are needed to substantiate associations between leukemia development and these hormones in the population of ALL children.


2015 ◽  
Vol 04 (02) ◽  
pp. 072-074 ◽  
Author(s):  
Adel A. Hagag ◽  
Mohamed A. Saad ◽  
Sohair A. Mohamed

Abstract Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, representing one-third of pediatric cancers. Thymidine kinase-1 (TK-1) is expressed in proliferating cells so elevated TK-1 indicates active tumor growth. Objective: To study the clinical significance of TK-1 in children with ALL. Patients and Methods: This study was carried out on 40 children with newly diagnosed ALL who were admitted to Oncology Unit, Pediatric department, Tanta University (26 males and 14 females) with their ages ranged from 4 to 10 years and 30 healthy children of matched age and sex as a control group. For all patients the following were done: Complete blood picture, bone marrow examination, immunophenotyping and TK-1 serum levels. Results: Mean TK-1 level was significantly higher in patients at diagnosis than controls and significantly higher in patients with unfavorable outcome than patients with favorable outcome. Mean TK-1 level was significantly higher in patients in relapse than patients in remission and controls. No significant differences in mean TK-1 level between patients in remission and controls. There were statistically significant differences in disease free survival and overall survival between patients with favorable and unfavorable outcome. Conclusion: From this study we concluded that TK is a helpful marker in diagnosis and follow-up of patients with ALL. Recommendations: Thymidine kinase-1 should be routinely assessed at diagnosis and during follow-up in ALL patients for better diagnostic and prognostic assessment and should be taken in consideration in designing future therapeutic strategies based on patients-specific risk factors.


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