Serum Levels of Soluble FLT3 Ligand in Patients with Active Multiple Myeloma Constitute Marker of Bone Marrow Plasma Cell Proliferative Activity

Crit Rev Oncog. 2017;22(3-4):255-262. doi: 10.1615/CritRevOncog.2018021355.

Abstract

The FLT3-ligand is a molecule implicated in hematopoiesis. The aim of the present study was to detect any possible connections between serum levels of FLT3-L and multiple myeloma (MM) proliferation markers, such as serum levels of interleukin-6 (IL-6), B-cell activating factor (BAFF), beta-2 microglobulin (B2M), CRP and LDH, as well the percentage of bone marrow infiltration and the plasma cells' proliferation marker Ki-67 PI. We measured the above parameters in 58 patients with active MM. All circulating markers were significantly higher in MM patients compared to controls (p < 0.001 for all cases), and all values were increasing in parallel with disease stage (p < 0.001 for all cases). Positive correlations between FLT3-L were noted with serum levels of BAFF (p < 0.003), IL-6 (p < 0.002), CRP (p < 0.0001), LDH (p < 0.001), and BM Ki-67 PI (p = 0.012), whereas only trends of correlation were noted with the B2M value and the percentage of infiltration. It seems that the increased serum levels of circulating FLT3-L, in parallel with MM activity, reflect their increased presence in the bone marrow microenvironment, probably as an effect of increased angiogenesis and myelosuppression. Consequently, they are potential markers of disease activity.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Bone Marrow Cells / metabolism*
  • Cell Proliferation / physiology*
  • Female
  • Humans
  • Male
  • Membrane Proteins / blood*
  • Middle Aged
  • Multiple Myeloma / blood*
  • Plasma Cells / metabolism*
  • Tumor Microenvironment / physiology

Substances

  • Biomarkers, Tumor
  • Membrane Proteins
  • flt3 ligand protein