Potential role of FLT3-ligand in the angiogenic process of multiple myeloma

Leuk Res. 2015 Dec;39(12):1467-72. doi: 10.1016/j.leukres.2015.10.009. Epub 2015 Oct 20.


The aim of the study was to evaluate serum levels of FLT3-ligand (FLT3-L), a soluble molecule in bone marrow (BM), participating actively in hematopoiesis, in relation with angiogenic factors in multiple myeloma (MM) patients. We measured, in 70 patients with active MM and in 38 of them who responded to conventional therapy, serum levels of FLT3-L, along with known angiogenic factors, such as VEGF, endoglin, TNF-alpha and HGF (with ELISA) and BM microvascular density (MVD), estimating the immunohistochemical expression of CD31. All pre-treatment values were higher in active MM patients compared to controls (p<0.001 for all cases), in parallel with both International Staging System and Durie-Salmon stages (p<0.001 for all cases). Moreover, levels of FLT3-L correlated positively with all soluble angiogenic factors, as well with MVD (p<0.0001 for all cases). Post-treatment values of FLT3-L decreased significantly in responders to therapy (p<0.001). The underlying relation of MM angiogenesis with FLT3-L may result from the fact that BM microvasculature is a major source of FLT3-L, both in BM niche and probably in peripheral blood. Our results suggest that serum levels of FLT3-L may be used as angiogenic marker in MM patients.

Keywords: Angiogenesis; Cytokines; FLT3-L; Multiple myeloma.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD / blood
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Marrow / blood supply
  • Bortezomib / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Dexamethasone / administration & dosage
  • Endoglin
  • Female
  • Hepatocyte Growth Factor / blood
  • Humans
  • Male
  • Melphalan / administration & dosage
  • Membrane Proteins / blood
  • Membrane Proteins / physiology*
  • Microvessels / pathology
  • Middle Aged
  • Multiple Myeloma / blood supply*
  • Multiple Myeloma / drug therapy
  • Neoplasm Proteins / blood
  • Neoplasm Proteins / physiology*
  • Neoplasm Staging
  • Neovascularization, Pathologic / metabolism*
  • Prednisone / administration & dosage
  • Receptors, Cell Surface / blood
  • Tumor Necrosis Factor-alpha / analysis
  • Vascular Endothelial Growth Factor A / blood


  • Antigens, CD
  • ENG protein, human
  • Endoglin
  • HGF protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • Receptors, Cell Surface
  • Tumor Necrosis Factor-alpha
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • flt3 ligand protein
  • Hepatocyte Growth Factor
  • Bortezomib
  • Dexamethasone
  • Cyclophosphamide
  • Melphalan
  • Prednisone