title: The systemic cytokine environment is permanently altered in multiple myeloma.
abstract: Multiple myeloma (MM) is an incurable bone marrow malignancy of the B cell lineage. Utilizing multiplex Luminex technology we measured levels of 25 cytokines in the plasma of normal donors (n = 177), those with monoclonal gammopathy of undetermined significance (n = 8), and MM patients (n = 55) with either active disease, on treatment, or in remission. The cytokine levels were compared between normal donors and MM patients as well as between various phases of MM, and discriminant analysis was used to create a predictive classification model based on the differentially expressed cytokines. Evaluating age- and gender-dependence of cytokine expression, we determined that with age there is a shift toward a pro-inflammatory environment. Moreover, we observed a strong gender bias in cytokine expression. However, the profile of differentially expressed cytokines was heavily skewed toward an anti-inflammatory, pro-tumorigenic response in patients with MM. Significantly, our predictive model placed all patients in remission in the same category as those with active disease. Thus, our study demonstrates that the homeostasis of systemic cytokines is not restored when MM patients enter remission, suggesting that once an individual has cancer, the microenvironment is permanently altered and the system is primed for a relapse.
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Zheng
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Kyle
authors.initials: K
authors.lastname: Bemis
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Belch
authors.forename: Linda M
authors.initials: LM
authors.lastname: Pilarski
authors.forename: John E
authors.initials: JE
authors.lastname: Shively
authors.forename: Julia
authors.initials: J
authors.lastname: Kirshner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D016022:Case-Control Studies; D003165:Complement System Proteins / Q000276:immunology; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D016002:Discriminant Analysis; D005260:Female; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000097:blood / Q000276:immunology; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D010641:Phenotype; D012074:Remission Induction; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D003165:Complement System Proteins
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