title: Downregulated microRNA-148b in circulating PBMCs in chronic myeloid leukemia patients with undetectable minimal residual disease: a possible biomarker to discontinue imatinib safely.
abstract: BACKGROUND
  A subset of patients with chronic myeloid leukemia (CML) can sustain a complete molecular response after discontinuing imatinib mesylate (IM). We focused on microRNAs (miRNAs), with the aim of finding a molecular biomarker to discriminate which patients can safely and successfully discontinue IM use.
  
  
  METHODS
  To identify miRNAs that showed altered expression in patients who had discontinued IM (STOP-IM group), we first screened miRNA expression of peripheral blood mononuclear cells by using a TaqMan miRNA array on samples from five unselected patients from the STOP-IM group, seven CML patients receiving IM (IM group), and five healthy volunteers. We then performed miRNA quantification in 49 CML patients with deep molecular response. Mann-Whitney U and chi-square tests were used to determine statistical significance for comparisons between the control (healthy volunteers) and test groups (STOP-IM and IM groups). Multiple groups were compared by one-way analysis of variance.
  
  
  RESULTS
  Downregulation of miR-148b was noted in patients in the STOP-IM group and in a subset of the IM group. We then subdivided the IM patients into two groups: one with downregulated miR-148b expression (IM-1; less than the cut-off value) and the other without downregulated miR-148b expression (IM-2; greater than the cut-off value). The number of patients who had a sustained stable molecular response was significantly lower in IM-2 group. This group also had a significantly lower percentage of natural killer cells.
  
  
  CONCLUSIONS
  Downregulated miR-148 may contribute to immune surveillance in STOP-IM patients and may therefore have potential as additive information in managing CML patients undergoing treatment with IM.
authors.affiliation: Department of Molecular Oncology, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Junko H
authors.initials: JH
authors.lastname: Ohyashiki
authors.affiliation: Department of Molecular Oncology, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Ohtsuki
authors.affiliation: Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Izuru
authors.initials: I
authors.lastname: Mizoguchi
authors.affiliation: Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshimoto
authors.affiliation: Department of Hematology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Katagiri
authors.affiliation: Department of Molecular Oncology, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan ; Department of Molecular Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Umezu
authors.affiliation: Department of Hematology, Tokyo Medical University, Tokyo, Japan ; Department of Molecular Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007694:Killer Cells, Natural / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D018709:Statistics, Nonparametric
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: chronic myeloid leukemia; discontinuation; imatinib mesylate; miR-148b