title: Elevated serum monoclonal and polyclonal free light chains and interferon inducible protein-10 predicts inferior prognosis in untreated diffuse large B-cell lymphoma.
abstract: The detection of serum free light (FLC) is useful in the diagnosis of several hematological diseases. The role and biological relevance of monoclonal or polyclonal FLC elevations in predicting long-term outcome in diffuse large B-cell lymphoma (DLBCL) is unknown. We determined the relationship of the type of FLC elevations to outcome, tumor genotype, and pattern of serum cytokine elevations in 276 patients with untreated DLBCL. Elevated FLC was an adverse prognostic factor through 6 years of follow-up (monoclonal, Event free survival (EFS) HR = 3.56, 95% CI: 1.88-6.76, P <0.0001; polyclonal, EFS HR = 2.56, 95% CI: 1.50-4.38, P = 0.0006). About 73% of DLBCL tumors with monoclonal FLC elevations were activated B-cell type (ABC) versus 33% from patients with normal FLC. Only ABC-DLBCL lines secreted kappa FLC in vitro and this secretion could be inhibited by the NF-κB inhibitor bortezomib. Patients with monoclonal FLC had significantly (all P <0.001) increased serum levels of IL-12, sIL-2Rα, IL-1R, and IP-10. Patients with polyclonal elevations of FLC had higher levels of IL-6 (P = 0.033), IL-8 (P =0.025), sIL2Rα (P = 0.011), and IL-1R1 (P = 0.041). The combination of elevated FLC and a CXC superfamily chemokine IP-10 predicted a particularly inferior outcome characterized by late relapse. These increased abnormal FLC and cytokines are potentially useful biomarkers for prognosis and selecting agents for untreated DLBCL.
authors.affiliation: Division of Hematology, Department of Internal-Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Stenson
authors.forename: Cristine
authors.initials: C
authors.lastname: Allmer
authors.forename: William
authors.initials: W
authors.lastname: Macon
authors.forename: Brian
authors.initials: B
authors.lastname: Link
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Katzmann
authors.forename: Mamta
authors.initials: M
authors.lastname: Gupta
mesh_terms: D000911:Antibodies, Monoclonal / Q000097:blood* / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D045744:Cell Line, Tumor / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000097:blood*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D018572:Disease-Free Survival; D005803:Genes, Immunoglobulin; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood* / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007167:Immunotherapy; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000628:therapy; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000097:blood* / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016207:Cytokines; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D016328:NF-kappa B; D009363:Neoplasm Proteins; C507924:JAK2 protein, human; D053614:Janus Kinase 2