title: Up-regulated exosomal miRNA-140-3p in CML patients with musculoskeletal pain associated with discontinuation of tyrosine kinase inhibitors.
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.
authors.affiliation: Department of Hematology, Tokyo Medical University, 160-0023, Tokyo, Japan.|Department of Hematology, Erasmus Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Asano
authors.affiliation: Department of Hematology, Tokyo Medical University, 160-0023, Tokyo, Japan.|Department of Molecular Oncology, Institute of Medical Science, Tokyo Medical University, 160-0023, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Umezu
authors.affiliation: Department of Hematology, Tokyo Medical University, 160-0023, Tokyo, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Katagiri
authors.affiliation: Department of Hematology, Tokyo Medical University, 160-0023, Tokyo, Japan.|Department of Molecular Oncology, Institute of Medical Science, Tokyo Medical University, 160-0023, Tokyo, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kobayashi
authors.affiliation: Department of Hematology, Tokyo Medical University, 160-0023, Tokyo, Japan.
authors.forename: Tetsuzo
authors.initials: T
authors.lastname: Tauchi
authors.affiliation: Department of Hematology, Tokyo Medical University, 160-0023, Tokyo, Japan.
authors.forename: Moritaka
authors.initials: M
authors.lastname: Gotoh
authors.affiliation: Department of Hematology, Tokyo Medical University, 160-0023, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Hematology, Tokyo Medical University, 160-0023, Tokyo, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Okabe
authors.affiliation: Department of Molecular Oncology, Institute of Medical Science, Tokyo Medical University, 160-0023, Tokyo, Japan.
authors.forename: Junko H
authors.initials: JH
authors.lastname: Ohyashiki
authors.affiliation: Department of Hematology, Tokyo Medical University, 160-0023, Tokyo, Japan. ohyashik@rr.iij4u.or.jp.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
mesh_terms: D004791:Enzyme Inhibitors / Q000627:therapeutic use; D055354:Exosomes / Q000737:chemistry; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000150:complications*; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000502:physiology*; D059352:Musculoskeletal Pain / Q000097:blood*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D015854:Up-Regulation; D028761:Withholding Treatment
chemical_list: D004791:Enzyme Inhibitors; D035683:MicroRNAs; C544302:Mirn140 microRNA, human; D011505:Protein-Tyrosine Kinases
keywords: Chronic myeloid leukemia; Discontinuation of TKIs; Exosomes; Musculoskeletal pain; miRNA-140-3p