期刊
DRUG DESIGN DEVELOPMENT AND THERAPY
卷 8, 期 -, 页码 1151-1159出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S66812
关键词
chronic myeloid leukemia; imatinib mesylate; discontinuation; miR-148b
资金
- Private University Strategic Research Based Support Project: Epigenetics Research Project Aimed at General Cancer Cure Using Epigenetic Targets from MEXT (Ministry of Education, Culture, Sports, Science and Technology), Tokyo, Japan
- Grants-in-Aid for Scientific Research [25118727, 24790091] Funding Source: KAKEN
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. Conclusion: 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.
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