Glutamate dehydrogenase activity in lymphocytes of B-cell chronic lymphocytic leukaemia patients

Pajič, Tadej; Černelč, Peter; Briški, Alenka Sešek; Lejko-Zupanc, Tatjana; Malešič, Ivan

doi:10.1016/j.clinbiochem.2009.08.003

Cited by 7 publications

(8 citation statements)

References 48 publications

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“…S4). Glutamate dehydrogenase 1, mitochondrial (GLUD1) have previously been detected in B-cell chronic lymphoblastic leukemia and in peripheral blood cells from patients with infectious mononucleosis (30). In our cohort, GLUD1 was overexpressed in the AML samples (Fig.…”

Section: Sec-map Can Reveal Immunophenotype Of Leukemia Cellmentioning

confidence: 64%

“…The overexpression of drebrin (DBN1), which has previously been described in BCP-ALL and has been correlated with the ETV6-RUNX1 chromosomal translocation (21), was found in both T-ALL and BCP-ALL. Another marker, GLUD1, was overexpressed in AML, although it has previously been demonstrated in B-cell chronic lymphoblastic leukemia and in peripheral blood cells from patients with infectious mononucleosis (30). Ultimately, we tested whether we could resolve biologically significant protein signatures in cases with molecular lesions (ETV6-RUNX1 or hyperdiploidy).…”

Section: Discussionmentioning

confidence: 99%

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High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells

Kanderová

Kužílková

Stuchlý

et al. 2016

Molecular & Cellular Proteomics

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Acute leukemia is a disease pathologically manifested at both genomic and proteomic levels. Molecular genetic technologies are currently widely used in clinical research. In contrast, sensitive and high-throughput proteomic techniques for performing protein analyses in patient samples are still lacking. Here, we used a technology based on size exclusion chromatography followed by immunoprecipitation of target proteins with an antibody bead array (Size Exclusion Chromatography-Microsphere-based Affinity Proteomics, SEC-MAP) to detect hundreds of proteins from a single sample. In addition, we developed semi-automatic bioinformatics tools to adapt this technology for high-content proteomic screening of pediatric acute leukemia patients.To confirm the utility of SEC-MAP in leukemia immunophenotyping, we tested 31 leukemia diagnostic markers in parallel by SEC-MAP and flow cytometry. We identified 28 antibodies suitable for both techniques. Eighteen of them provided excellent quantitative correlation between SEC-MAP and flow cytometry (p < 0.05). Next, SEC-MAP was applied to examine 57 diagnostic samples from patients with acute leukemia. In this assay, we used 632 different antibodies and detected 501 targets. Of those, 47 targets were differentially expressed between at least two of the three acute leukemia subgroups. The CD markers correlated with immunophenotypic categories as expected. Acute leukemia (AL)1 is the most common childhood cancer, accounting for a quarter of all pediatric malignancies (1). Accumulated chromosomal translocations and mutations in proto-oncogenes alter proliferation, differentiation, apoptosis and death in developing hematogones, ultimately leading to the development of leukemia (2, 3). The most recent understanding of these cancer-related changes is based on molecular genetic studies that focused primarily on DNA and mRNA alterations. High-throughput molecular genetic technologies, such as mRNA expression profiling and next generation sequencing, are widely used in clinical research. These techniques can provide new classification schemes, define new prognostic subgroups and outline the background of some pathological mechanisms (2, 4, 5, 6, 7) but they cannot easily elucidate the functional consequences at the cellular level. Proteins are the principal carriers of cellular functions. Thus, From the ‡CLIP -Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2

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Section: Sec-map Can Reveal Immunophenotype Of Leukemia Cellmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells

Kanderová

Kužílková

Stuchlý

et al. 2016

Molecular & Cellular Proteomics

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“…The regulatory mechanism for GLDH with increasing age might be coupled with glutamine synthetase [14] . There is a difference in peripheral blood mononuclear cell GLDH activities by gender but not by age [11] .…”

Section: Introductionmentioning

confidence: 93%

“…The GLUD 1 gene (for housekeeping GLDH) is localized on human chromosome 10, is thermostable and is mainly located in hepatocytes, whereas GLUD 2 (for nerve tissue-specific) is localized on human chromosome X, is a thermolabile isoprotein and is mainly located in nerve tissues, testicles, retina and leukocytes [7,10,11] .…”

Section: Introductionmentioning

confidence: 99%

Glutamate Dehydrogenase Activity in Leukocytes and Ageing

Kravos

Malešič²

2010

Neurodegener Dis

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Background: Glutamate dehydrogenase (GLDH) is an intracellular enzyme normally located in mitochondria and the rough endoplasmic reticulum. The metabolism of neuroexcitotoxic glutamate is lowered in many neurodegenerative disorders. Objective: Defining the GLDH activity in leukocytes can provide indirect data about neurodegenerative processes in the brain. Method: We have developed our own method of defining the GLDH activity in leukocytes. Results: The GLDH activity was researched in the leukocytes of 130 healthy subjects (45 females, 85 males). The mean catalytic activity was 0.618 ± 0.380 µkat/g. The highest values were discovered in <30-year-old persons: 0.772 ± 0.434 µkat/g (0.712 ± 0.406 µkat/g in men, 0.934 ± 0.5 µkat/g in women). The GLDH activity decreases more slowly in the 30- to 60-year age group, yet evidently more rapidly afterwards, particularly in men, where the activity drops to 0.333 µkat/g and in women to 0.414 µkat/g. The older persons had a lower leukocyte GLDH activity than the younger ones (ANOVA, p = 0.000). Conclusion: Gradual decrease in GLDH activity may be one of the key factors for neurodegenerative ageing processes.

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“…Its production is controlled by glutaminase (GLS), while glutamate dehydrogenase (GDH) and glutamate decarboxylase catalyze its degradation [17, 18]. …”

Section: Introductionmentioning

confidence: 99%

The Markers of Glutamate Metabolism in Peripheral Blood Mononuclear Cells and Neurological Complications in Lung Cancer Patients

et al. 2016

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Objective. To evaluate the involvement of glutamate metabolism in peripheral blood mononuclear cells (PBMC) in the development of neurological complications in lung cancer and during chemotherapy. Methods. The prospective study included 221 lung cancer patients treated with chemotherapeutics. Neurological status and cognitive functions were evaluated at baseline and after 6-month follow-up. Glutamate level, the activities of glutaminase- (GLS-) glutamate synthetizing enzyme, glutamate dehydrogenase (GDH), and glutamate decarboxylase catalyzing glutamate degradation were analyzed in PBMC and in sera of lung cancer patients by means of spectrophotometric and colorimetric methods. Results. Chemotherapy of lung neoplasms induced increase of glutamate content in PBMC and its concentration in serum increased the activity of GDH in PBMC and decreased activity of glutaminase in PBMC. The changes in glutamate metabolism markers were associated with initial manifestation of neurological deficit in lung cancer patients and with new symptoms, which appear as a complication of chemotherapy. Moreover, the analyzed parameters of glutamate control correlated with a spectrum of cognitive functions measures in lung cancer patients. Conclusion. We have demonstrated dysregulation in glutamate and glutamate metabolism controlling enzymes as promising indicators of risk for chemotherapy-induced neurological complications in lung cancer patients with particular emphasis on cognitive impairment.

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Glutamate dehydrogenase activity in lymphocytes of B-cell chronic lymphocytic leukaemia patients

Cited by 7 publications

References 48 publications

High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells

High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells

Glutamate Dehydrogenase Activity in Leukocytes and Ageing

The Markers of Glutamate Metabolism in Peripheral Blood Mononuclear Cells and Neurological Complications in Lung Cancer Patients

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