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Type: Journal article
Title: Plasma adiponectin levels are markedly elevated in imatinib-treated chronic myeloid leukemia (CML) patients: A mechanism for improved insulin sensitivity in Type 2 diabetic CML patients?
Author: Fitter, S.
Vandyke, K.
Schultz, C.
White, D.
Hughes, T.
Zannettino, A.
Citation: Journal of Clinical Endocrinology and Metabolism, 2010; 95(8):3763-3767
Publisher: Endocrine Society
Issue Date: 2010
ISSN: 0021-972X
Statement of
Stephen Fitter, Kate Vandyke, Christopher G. Schultz, Deborah White, Timothy P. Hughes, and Andrew C. W. Zannettino
Abstract: Context: The mechanism(s) by which imatinib improves glycemic control in chronic myeloid leukemia (CML) patients with type 2 diabetes remains unclear. Objective: Adiponectin is an important regulator of insulin sensitivity that is secreted exclusively by adipocytes. We previously reported that imatinib promotes adipocytic differentiation of mesenchymal stromal cells. We therefore hypothesized that imatinib therapy would be associated with an increase in peripheral and intramedullary adiposity and elevated plasma adiponectin levels. Research Design and Methods: Adiponectin levels in CML patient plasma, at diagnosis and then during imatinib mesylate therapy, was measured using an ELISA. Adiponectin multimers in plasma were analyzed using nondenaturing PAGE and immunoblotting. Intramedullary adiposity and adipose tissue mass was determined using histomorphometry and dual-energy X-ray absorptiometry, respectively. Results: In CML patients, an increase in intramedullary and peripheral adiposity was observed after 6 months of imatinib therapy and plasma adiponectin levels, in the form of high- and low-molecular-weight complexes, were elevated 3-fold, compared with pretreatment levels, after 3, 6, and 12 months of therapy. Conclusions: Elevated adiponectin levels in imatinib-treated CML patients provide a possible mechanism for improved glucose and lipid metabolism reported for some imatinib-treated patients.
Keywords: Humans
Insulin Resistance
Protein Kinase Inhibitors
Absorptiometry, Photon
Blotting, Western
Enzyme-Linked Immunosorbent Assay
Treatment Outcome
Analysis of Variance
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Imatinib Mesylate
Rights: Copyright © 2010 by The Endocrine Society
DOI: 10.1210/jc.2010-0086
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