title: Expression patterns of leptin receptor (OB-R) isoforms and direct in vitro effects of recombinant leptin on OB-R, leptin expression and cytokine secretion by human hematopoietic malignant cells.
abstract: Several studies have implicated leptin in the pathophysiology of neoplasias. We investigated the direct effect of leptin on malignant hematopoietic tissue that included: primary acute myeloid leukemia (AML) cells, leukemic cell lines and bone marrow biopsies from multiple myeloma (MM) patients. PBMC, T-cells, B-cells and monocytes from healthy subjects served as controls. We defined the patterns of OB-R isoform expression in AML cells and leukemic cell lines in comparison to control cells by RT-PCR. rLeptin upregulated the expression of OB-R and endogenous leptin in AML blasts and certain cell lines but not in control cells. Cytometric Bead Array analysis of pro- and anti-inflammatory cytokines showed that rleptin upregulates IL-6 secretion by AML cells, various cytokines by the leukemic cell lines tested and IL-10 secretion by control PBMC, contributed by monocytes. Western immunoblotting revealed that the effect of rleptin was independent of JAK-2/phospho-JAK-2 protein levels. Finally, MM biopsies stained positive for leptin and, to a lesser extend, OB-R. Immunoreactivity was confined mostly to the nucleus of the myeloma cells. Normal myelocytes, promyelocytes and megakaryocytes stained weakly positive, and erythroid cells were constantly negative. We propose that the leptin/OB-R system is strongly and directly involved in supporting the growth of hematopoietic malignancies.
authors: Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece. mouzaki@med.upatras.gr
authors: Athanasia
authors: A
authors: Mouzaki
authors: Ioannis
authors: I
authors: Panagoulias
authors: Zoe
authors: Z
authors: Dervilli
authors: Vassiliki
authors: V
authors: Zolota
authors: Panagiota
authors: P
authors: Spadidea
authors: Maria
authors: M
authors: Rodi
authors: Fotios P
authors: FP
authors: Panitsas
authors: Eleni
authors: E
authors: Lagadinou
authors: Anne-Lise
authors: AL
authors: de Lastic
authors: Tassos
authors: T
authors: Georgakopoulos
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D020738:Leptin / Q000235:genetics / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute; D009000:Monocytes / Q000276:immunology; D020033:Protein Isoforms; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; D020738:Leptin; D020033:Protein Isoforms; D054411:Receptors, Leptin; D011994:Recombinant Proteins