title: All in the family: Clueing into the link between metabolic syndrome and hematologic malignancies.
abstract: Metabolic syndrome constitutes a constellation of findings including central obesity, insulin resistance/type 2 diabetes mellitus (DM), dyslipidemia and hypertension. Metabolic syndrome affects 1 in 4 adults in the United States and is rapidly rising in prevalence, largely driven by the dramatic rise in obesity and insulin resistance/DM. Being central to the development of metabolic syndrome and its other related diseases, much focus has been placed on identifying the mitogenic effects of obesity and insulin resistance/DM as mechanistic clues of the link between metabolic syndrome and cancer. Pertinent mechanisms identified include altered lipid signaling, adipokine and inflammatory cytokine effects, and activation of PI3K/Akt/mTOR and RAS/RAF/MAPK/ERK pathways via dysregulated insulin/insulin-like growth factor-1 (IGF-1) signaling. Through variable activation of these multiple pathways, obesity and insulin resistance/DM pre-dispose to hematologic malignancies, imposing the aggressive and chemo-resistant phenotypes typically seen in cancer patients with underlying metabolic syndrome. Growing understanding of these pathways has identified druggable cancer targets, rationalizing the development and testing of agents like PI3K inhibitor idelalisib, mTOR inhibitors everolimus and temsirolimus, and IGF-1 receptor inhibitor linsitinib. It has also led to exploration of obesity and diabetes-directed therapies including statins and oral hypoglycemic for the management of metabolic syndrome-related hematologic neoplasms.
authors.affiliation: Division of Hematology, Oncology and Cell Therapy, Rush University Medical Center, 1725 W Harrison Street, Suite 809, Chicago, IL 60612, United States. Electronic address: reem_karmali@rush.edu.
authors.forename: Reem
authors.initials: R
authors.lastname: Karmali
authors.affiliation: Division of Hematology, Oncology and Cell Therapy, Rush University Medical Center, 1725 W Harrison Street, Suite 809, Chicago, IL 60612, United States. Electronic address: Andrew_dalovisio@rush.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dalovisio
authors.affiliation: Department of Pathology, Rush Proteomics and Biomarker Development Core, Rush University Medical Center, 1735 W Harrison Street, Suite 554, Chicago, IL 60612, United States; Department of Biochemistry, Rush Proteomics and Biomarker Development Core, Rush University Medical Center, 1735 W Harrison Street, Suite 554, Chicago, IL 60612, United States. Electronic address: Jeffrey_A_borgia@rush.edu.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Borgia
authors.affiliation: Division of Hematology, Oncology and Cell Therapy, Rush University Medical Center, 1725 W Harrison Street, Suite 809, Chicago, IL 60612, United States. Electronic address: Parameswaran_Venugopal@rush.edu.
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Venugopal
authors.affiliation: Division of Endocrinology, Rush University Medical Center, Cohn Building Room 226, 1735 W Harrison Street, Chicago, IL 60612, United States. Electronic address: brian_w_kim@rush.edu.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Kim
authors.affiliation: Division of Hematology, Oncology and Cell Therapy, Rush University Medical Center, 1725 W Harrison Street, Suite 809, Chicago, IL 60612, United States. Electronic address: kelly_grant@rush.edu.
authors.forename: Kelly
authors.initials: K
authors.lastname: Grant-Szymanski
authors.affiliation: Medical College of Wisconsin, 9200 W. Wisconsin Ave., Clinical Cancer Center, Milwaukee, WI 53226, United States. Electronic address: phari@mcw.edu.
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Hari
authors.affiliation: Case Western Reserve University, Novel Cell Therapy, 11100 Euclid Ave., Wearn Bldg. Room 341, Cleveland, OH 44106-5089, United States. Electronic address: hillard.lazarus@case.edu.
authors.forename: Hillard
authors.initials: H
authors.lastname: Lazarus
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology* / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000150:complications / Q000453:epidemiology* / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism; D024821:Metabolic Syndrome / Q000150:complications / Q000453:epidemiology* / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000453:epidemiology* / Q000378:metabolism; D015398:Signal Transduction
keywords: Adipokines; Dyslipidemia; Hematologic malignancy; IGF-1; Inflammation; Insulin resistance; Insulin signaling; Lipid signaling; Metabolic syndrome; Metformin; Obesity; Reactive oxygen species