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      Leptin and its receptor in glucose metabolism of T-cell lymphoma

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          Abstract

          T-cell lymphoma (TCL) is a group of heterogeneous disorders with a poor response to conventional treatment. In order to identify novel therapeutic targets, the present study investigated the effect of leptin and its receptor on glucose metabolism in TCL. The expression of the leptin receptor (ObR), and glucose transporter (Glut)1 and 4 was detected in TCL and reactive lymphoid hyperplasia (RLH) tissues by immunohistochemical analysis. A higher level of ObR expression was observed in the TCL tissues than in the RLH tissues (58.3 vs. 22.2%; P=0.012), and ObR overexpression was associated with high expression of Glut1 (P=0.007). In vitro analysis using the human TCL MOLT-3 cell line demonstrated that leptin stimulated cell glucose uptake via promoting recruitment and expression of Glut1, effects which were abolished by ObR-specific small interfering RNA (siRNA). Additionally, MOLT-3 cell viability was also increased following leptin treatment. ObR-specific siRNA abolished these responses. In conclusion, these results suggested that leptin serves a critical role in TCL glucose uptake via the ObR.

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          A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project.

          W.C. Chan, F. Cavalli, P Jacobs … (1997)
          The recognition of several new types of non-Hodgkin's lymphoma (NHL) in recent years has led to proposals for changing lymphoma classifications, including a new proposal put forth by the International Lymphoma Study Group (ILSG). However, the clinical significance of the new entities and the practical utility of this new proposal have not been studied. Therefore, we performed a clinical evaluation of the ILSG classification. A cohort of 1,403 cases of NHL was organized at nine study sites around the world and consisted of consecutive patients seen between 1988 and 1990 who were previously untreated. A detailed protocol for histologic and clinical analysis was followed at each site, and immunologic characterization as to T- or B-cell phenotype was required. Five expert hematopathologists visited the sites and each classified each case using the ILSG classification. A consensus diagnosis was also reached in each case, and each expert rereviewed a 20% random sample of the cases. Clinical correlations and survival analyses were then performed. A diagnosis of NHL was confirmed in 1,378 (98.2%) of the cases. The most common lymphoma types were diffuse large B-cell lymphoma (31%) and follicular lymphoma (22%), whereas the new entities comprised 21% of the cases. Diagnostic accuracy was at least 85% for most of the major lymphoma types, and reproducibility of the diagnosis was 85%. Immunophenotyping improved the diagnostic accuracy by 10% to 45% for a number of the major types. The clinical features of the new entities were distinctive. Both the histologic types and the patient characteristics as defined by the International Prognostic Index predicted for patient survival. In conclusion we found that the ILSG classification can be readily applied and identifies clinically distinctive types of NHL. However, for clinical application, prognostic factors as defined by the International Prognostic Index must be combined with the histologic diagnosis for appropriate clinical decisions.
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            WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview.

            E. Sabattini, F Bacci, C Sagramoso … (2010)
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              Leptin regulates proinflammatory immune responses.

              T. Lin, B H Bulkley, G Bulkley … (1998)
              Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity and mortality. Decreased expression of leptin or of functional leptin receptors results in hyperphagia, decreased energy expenditure, and obesity. It is unclear, however, whether defective leptin-dependent signal transduction directly promotes any of the conditions that frequently complicate obesity. Abnormalities in tumor necrosis factor alpha expression have been noted in each of the above comorbid conditions, so leptin deficiency could promote these complications if leptin had immunoregulatory activity. Studies of rodents with genetic abnormalities in leptin or leptin receptors revealed obesity-related deficits in macrophage phagocytosis and the expression of proinflammatory cytokines both in vivo and in vitro. Exogenous leptin up-regulated both phagocytosis and the production of proinflammatory cytokines. These results identify an important and novel function for leptin: up-regulation of inflammatory immune responses, which may provide a common pathogenetic mechanism that contributes to several of the major complications of obesity.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Oncol Lett
                Journal ID (iso-abbrev): Oncol Lett
                Journal ID (publisher-id): OL
                Title: Oncology Letters
                Publisher: D.A. Spandidos
                ISSN (Print): 1792-1074
                ISSN (Electronic): 1792-1082
                Publication date (Print): November 2018
                Publication date (Electronic): 23 August 2018
                Publication date PMC-release: 23 August 2018
                Volume: 16
                Issue: 5
                Pages: 5838-5846
                Affiliations
                [1 ]Department of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China
                [2 ]Department of Hematology, Tai'an City Central Hospital, Tai'an, Shandong 271000, P.R. China
                [3 ]Department of Gastroenterology, Tai'an City Central Hospital, Tai'an, Shandong 271000, P.R. China
                Author notes
                Correspondence to: Dr Xin Wang, Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, P.R. China, E-mail: xinw007@ 123456126.com
                Article
                Publisher ID: OL-0-0-9356
                DOI: 10.3892/ol.2018.9356
                PMC ID: 6176461
                SO-VID: 1606605b-c3c3-4176-bb2d-58e258e55245
                Copyright © Copyright: © Han et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Date received : 12 May 2017
                Date accepted : 23 February 2018
                Categories
                Subject: Articles

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: t-cell lymphoma,leptin,leptin receptor,glucose transporter 1,glucose uptake
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: t-cell lymphoma, leptin, leptin receptor, glucose transporter 1, glucose uptake

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