Monokine induced by interferon gamma (MIG/CXCL9) is an independent prognostic factor in newly diagnosed myeloma

Leuk Lymphoma. 2016 Nov;57(11):2516-25. doi: 10.3109/10428194.2016.1151511. Epub 2016 Mar 21.

Abstract

Immune suppression is a hallmark of multiple myeloma (MM), but data on soluble factors involved in the fate of immune effector cells are limited. The CXCR3-binding chemokine monokine induced by interferon-gamma (MIG/CXCL9) has been associated with tumor progression, immune escape, and angiogenesis in several malignancies. We here aimed to evaluate the prognostic relevance of MIG in MM. MIG serum levels were significantly elevated in newly diagnosed MM patients (n = 105) compared to patients with monoclonal gammopathy of undetermined significance (MGUS; n = 17) and healthy controls (n = 37). MIG expression in stromal compartments but not purified MM cells correlated with serum levels. High MIG serum levels were significantly associated with established prognostic markers (international staging system: R = 0.25, p = 0.001; age: R = 0.47, p < 0.0001; lactate-dehydrogenase: R = 0.34, p = 0.0005) and poor overall survival (OS) (median OS 17.0 months vs. not reached, p < 0.001). A similar association was found for CXCL10 and CXCL11. Multivariate regression analysis indicated MIG as an independent prognostic factor of OS.

Keywords: CXCL10; CXCL11; CXCL9; MIG; multiple myeloma; prognosis.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Chemokine CXCL9 / blood
  • Chemokine CXCL9 / metabolism*
  • Chemokines / metabolism
  • Combined Modality Therapy
  • Female
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / metabolism*
  • Multiple Myeloma / mortality*
  • Multiple Myeloma / therapy
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Protein Binding
  • Receptors, CXCR3 / metabolism
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers
  • CXCL9 protein, human
  • CXCR3 protein, human
  • Chemokine CXCL9
  • Chemokines
  • Receptors, CXCR3