Macrophage inflammatory protein 1 alpha (MIP-1α) may be associated with poor outcome in patients with extranodal NK/T-cell lymphoma

Hematol Oncol. 2017 Sep;35(3):310-316. doi: 10.1002/hon.2283. Epub 2016 Feb 29.

Abstract

The macrophage inflammatory protein 1α (MIP-1α) is anticipated to have a role in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) because the expression of MIP-1α is related to Epstein-Barr virus (EBV) latency in EBV-related non-Hodgkin lymphoma cells. Thus, we measured the serum level of MIP-1α in 69 patients with ENKTL using frozen serum samples that were archived at diagnosis. As serum level of MIP-1α was not detectable in 19 patients (range: 0-24.37 pg/mL), patients were dichotomized into positive (n = 50) and negative (n = 19) MIP-1α groups according to the presence of detectable level of MIP-1α in serum. MIP-1α-positive group showed a significantly poor overall survival (OS) in comparison with the MIP-1α-negative group (p = 0.004). In the subgroup analysis, the positivity of MIP-1α was significantly associated with OS in patients with stage IIIE/IV and a detectable level of EBV DNA (p = 0.002 and 0.032, respectively). Multivariate analysis also showed that the positivity of MIP-1α was independently associated with worse OS together with bone marrow involvement (p = 0.002). An in vitro study with patient-derived ENKTL tumour cells showed the expression of CCR1 and CCR5 on the surface of tumour cells (28% and 14%, respectively) , and the addition of MIP-1α to the culture media of tumour cells increased cell growth supporting the negative impact of MIP-1α on the prognosis of ENKTL patients. In conclusion, serum levels of MIP-1α could predict survival outcomes in patients with ENKTL. Therefore, MIP-1α should be considered for prognostication and a potential therapeutic target. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: MIP-1α; chemokine; extranodal NK/T-cell lymphoma.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor*
  • Cell Proliferation
  • Chemokine CCL3 / blood
  • Chemokine CCL3 / metabolism*
  • Female
  • Humans
  • Lymphoma, Extranodal NK-T-Cell / diagnosis
  • Lymphoma, Extranodal NK-T-Cell / metabolism*
  • Lymphoma, Extranodal NK-T-Cell / mortality*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Receptors, CCR1 / metabolism
  • Survival Analysis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Chemokine CCL3
  • Receptors, CCR1