Abstract
Recently, leptin has been shown to play a regulatory role for differentiation within the myeloid and erythroid cell lineage, whereas results of its regulatory effects on lymphocytes and related tumor cells have been contradictory. To investigate whether leptin plays a role in acute lymphoblastic leukemia (ALL), we investigated the levels of leptin in plasma with enzymelinked immunosorbent assays and the expression of the leptin receptor on malignant lymphoblasts with reverse transcriptase polymerase chain reaction (RT-PCR). At diagnosis, the leptin levels of bone marrow-derived plasma in children with ALL were found to be significantly lower than the levels of healthy control subjects (0.92 ± 0.79 ng/mL versus 3.01 ± 2.27 ng/mL, respectively). Notably, at complete hematologic remission (at day 33 of chemotherapy), leptin levels had normalized to 2.6 ± 2.4 ng/mL. To elucidate the underlying mechanism of this phenomenon, we analyzed the expression of the leptin receptor on the mononuclear cell populations of the patients. RT-PCR analysis revealed gene expression rates of 33% at diagnosis versus 71% at remission, compared with 100% for healthy control subjects. Results of immunohistochemical staining supported these findings by showing that the tumor clones themselves do not express the leptin receptor. Finally, some hypotheses that might explain the decrease of leptin levels in the presence of the tumor clone are discussed.Int J Hematol. 2002;76:446-452.
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References
Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin stimulates proliferation and activation of human circulating monocytes.Cell Immunol. 1999;194:6–11.
Gainsford T, Willson TA, Metcalf D, et al. Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells.Proc Natl Acad Sci U S A. 1996;93:14564–14568.
Umemoto Y, Tsuji K, Yang FC, et al. Leptin stimulates the proliferation of murine myelocytic and primitive hematopoietic progenitor cells.Blood. 1997;90:3438–3443.
Bennett BD, Solar GP, Yuan JQ,Mathias J, Thomas GR, Matthews W. A role for leptin and its cognate receptor in hematopoiesis.Curr Biol. 1996;6:1170–1180.
Cioffi JA, Shafer AW, Zupancic TJ, et al. Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction.Nat Med. 1996;2:585–589.
Nakao T, Hino M, Yamane T, Nishizawa Y, Morii H, Tatsumi N. Expression of the leptin receptor in human leukaemic blast cells.Br J Haematol. 1998;102:740–745.
Fantuzzi G, Faggioni R. Leptin in the regulation of immunity, inflammation, and hematopoiesis.J Leukoc Biol. 2000;68:437–446.
Martin-Romero C, Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin enhances activation and proliferation of human circulating T lymphocytes.Cell Immunol. 2000;199:15–24.
Laharrague P, Truel N, Fontanilles AM, Corberand JX, Penicaud L, Casteilla L. Regulation by cytokines of leptin expression in human bone marrow adipocytes.Horm Metab Res. 2000;32:381–385.
Wex H, Vorwerk P, Mohnike K, et al. Elevated serum levels of IGFBP-2 found in children suffering from acute leukaemia is accompanied by the occurrence of IGFBP-2 mRNA in the tumour clone.Br J Cancer. 1998;78:515–520.
Rothe G, Schmitz G. Consensus protocol for the flow cytometric immunophenotyping of hematopoietic malignancies: Working Group on Flow Cytometry and Image Analysis.Leukemia. 1996;10: 877–895.
Gainsford T, Alexander WS. A role for leptin in hemopoieses?Mol Biotechnol. 1999;11:149–158.
Lopez-Soriano J, Carbo N, Tessitore L, Lopez-Soriano FJ, Argiles JM. Leptin and tumor growth in rats.Int J Cancer. 1999;81:726–729.
Tessitore L, Vizio B, Jenkins O, et al. Leptin expression in colorectal and breast cancer patients.Int J Mol Med. 2000;5:421–426.
Konopleva M, Mikhail A, Estrov Z, et al. Expression and function of leptin receptor isoforms in myeloid leukemia and myelodysplastic syndromes: proliferative and anti-apoptotic activities.Blood. 1999;93:1668–1676.
Gottschling-Zeller H, Birgel M, Scriba D, Blum WF, Hauner H. Depot-specific release of leptin from subcutaneous and omental adipocytes in suspension culture: effect of tumor necrosis factoralpha and transforming growth factor-beta1.Eur J Endocrinol. 1999;141:436–442.
Fawcett RL, Waechter AS, Williams LB, et al. Tumor necrosis factor-alpha inhibits leptin production in subcutaneous and omental adipocytes from morbidly obese humans.J Clin Endocrinol Metab. 2000;85:530–535.
Kurzrock R.The role of cytokines in cancer-related fatigue.Cancer. 2001;92(suppl):1684–1688.
Tisdale MJ. Wasting in cancer.J Nutr. 1999;129(suppl 1S): 243S-246S.
Matthys P, Billiau A. Cytokines and cachexia.Nutrition. 1997;13: 763–770.
Lerario DD, Ferreira SR, Miranda WL, Chacra AR. Influence of dexamethasone and weight loss on the regulation of serum leptin levels in obese individuals.Braz J Med Biol Res. 2001;34: 479–487.
Nishiyama M, Makino S, Suemaru S, et al. Glucocorticoid effects on the diurnal rhythm of circulating leptin levels.Horm Res. 2000; 54:69–73.
Masuzaki H, Ogawa Y, Hosoda K, et al. Glucocorticoid regulation of leptin synthesis and secretion in humans: elevated plasma leptin levels in Cushing’s syndrome.J Clin Endocrinol Metab. 1997;82: 2542–2547.
Laferrere B, Fried SK, Hough K, Campbell SA, Thornton J, Pi-Sunyer FX. Synergistic effects of feeding and dexamethasone on serum leptin levels.J Clin Endocrinol Metab. 1998;83:3742–3745.
Heuck C, Wolthers OD. Serum leptin in children with asthma treated with inhaled budesonide.Respir Med. 1999;93:268–271.
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Wex, H., Ponelis, E., Wex, T. et al. Plasma Leptin and Leptin Receptor Expression in Childhood Acute Lymphoblastic Leukemia. Int J Hematol 76, 446–452 (2002). https://doi.org/10.1007/BF02982810
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DOI: https://doi.org/10.1007/BF02982810