High Levels of FLT3-ligand in Bone Marrow and Peripheral Blood of Patients With Advanced Multiple Myeloma

PLoS One. 2017 Jul 20;12(7):e0181487. doi: 10.1371/journal.pone.0181487. eCollection 2017.

Abstract

Introduction: Multiple myeloma (MM) is still incurable due to resistance against various therapies. Thus, the identification of biomarkers predicting progression is urgently needed. Here, we evaluated four biomarkers in bone marrow and peripheral blood of MM patients for their prognostic significance.

Materials & methods: Bone marrow- and peripheral blood plasma levels of FLT3-L, soluble TIE2, endostatin, and osteoactivin were determined in patients with monoclonal gammopathy of undetermined significance (MGUS, n = 14/n = 4), patients with newly diagnosed MM (NDMM, n = 42/n = 31) and patients with relapsed/refractory MM (RRMM, n = 27/n = 16) by sandwich ELISA.

Results: Median FLT3-L expression increased from MGUS (58.77 pg/ml in bone marrow; 80.40 pg/ml in peripheral blood) to NDMM (63.15 pg/ml in bone marrow; 85.05 pg/ml in peripheral blood) and was maximal in RRMM (122 pg/ml in bone marrow; 160.47 pg/ml in peripheral blood; NDMM vs. RRMM p<0.001). A cut-off value of FLT3-L >92 pg/ml in bone marrow and >121 pg/ml in peripheral blood was associated with relapse or refractoriness in MM patients. FLT3-L was found to be a high predictive marker for discrimination between NDMM and RRMM as well in bone marrow as in peripheral blood (AUC 0.75 in bone marrow; vs 0.84 in peripheral blood).

Conclusion: High levels of FLT3-L in bone marrow and peripheral blood of MM patients identify patients with progressive disease and are associated with relapse or refractoriness in MM patients. FLT3-L could be useful as a marker to identify RRMM patients and should be evaluated as target for future therapies.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Bone Marrow / metabolism*
  • Diagnosis, Differential
  • Endostatins / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Multiple Myeloma / metabolism*
  • Prognosis
  • ROC Curve
  • Receptor, TIE-2 / metabolism
  • Recurrence

Substances

  • Biomarkers, Tumor
  • Endostatins
  • GPNMB protein, human
  • Membrane Glycoproteins
  • Membrane Proteins
  • flt3 ligand protein
  • Receptor, TIE-2

Grant support

The authors received no specific funding for this work.