Up-regulated exosomal miRNA-140-3p in CML patients with musculoskeletal pain associated with discontinuation of tyrosine kinase inhibitors

Int J Hematol. 2017 Apr;105(4):419-422. doi: 10.1007/s12185-017-2199-z. Epub 2017 Feb 14.

Abstract

We analyzed the exosomal miRNA from peripheral blood from CML patients with musculoskeletal pain after stopping tyrosine kinase inhibitors to identify possible factors related to this manifestation. Exosomal miRNA profiling using TaqMan low-density array revealed that exosomal miR-140-3p was significantly elevated in CML patients showing musculoskeletal pain, when compared to those without such pain (P = 0.0336) or healthy individuals (P = 0.0022). All five CML patients with musculoskeletal pain and increased exosomal miR-140-3p levels sustained deep molecular responses: four of them achieved symptom relief and a significant decrease in exosomal miR-140-3p levels was evident. Because exosomal miR-140-3p is considered to have an inflammation-associated biological function in airway smooth muscle cells and targets Myomarker muscle-specific transmembrane protein, it appears that its overexpression in circulating exosomal miR-140-3p may have some role in the mechanism underlying self-limited musculoskeletal pain.

Keywords: Chronic myeloid leukemia; Discontinuation of TKIs; Exosomes; Musculoskeletal pain; miRNA-140-3p.

MeSH terms

  • Enzyme Inhibitors / therapeutic use
  • Exosomes / chemistry
  • Female
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications*
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / physiology*
  • Musculoskeletal Pain / blood*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Up-Regulation
  • Withholding Treatment

Substances

  • Enzyme Inhibitors
  • MicroRNAs
  • Mirn140 microRNA, human
  • Protein-Tyrosine Kinases