High bone marrow miR-19b level predicts poor prognosis and disease recurrence in de novo acute myeloid leukemia

Gene. 2018 Jan 15;640:79-85. doi: 10.1016/j.gene.2017.10.034. Epub 2017 Oct 12.

Abstract

Oncogenic role of miR-19 family has been identified in human cancers especially in lymphoid malignancies. However, to date, little studies investigated the role of miR-19 family in myeloid malignancies. Herein, we examined miR-19a/b expression and explored its clinical significance in de novo acute myeloid leukemia (AML). The detection of miR-19a/b expression was performed by real-time quantitative PCR in bone marrow mononuclear cells of 113 patients and 42 healthy donors. Both miR-19a/b levels were significantly increased in AML patients in contrast to controls. Patients with miR-19a/b overexpression were more frequently occurred in female, and had an older age. Moreover, cases with miR-19a overexpression had a higher frequency of U2AF1, C-KIT and CEBPA mutations, whereas miR-19b overexpressed cases harbored U2AF1 and IDH1/2 mutations. There was no significant association of miR-19a overexpression with complete remission (CR) rate and overall survival (OS) among whole-cohort AML, non-M3 AML, and cytogenetically normal AML (CN-AML). However, although miR-19b overexpression was not correlated with CR rate, patients with miR-19b overexpression presented significantly shorter OS in whole-cohort AML and a trend in non-M3 AML and CN-AML patients. Importantly, our data also showed that miR-19a/b expression level at CR phase was lower than diagnosis time, and was returned to primary level even higher when at relapse phase. Our findings revealed that miR-19a/b overexpression were frequent events in de novo AML patients. Moreover, up-regulation of miR-19b expression was associated with poor prognosis and disease recurrence in AML.

Keywords: Acute myeloid leukemia (AML); Prognosis; miR-19.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Bone Marrow / metabolism*
  • Bone Marrow / pathology
  • Case-Control Studies
  • Child
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Mutation
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • ROC Curve
  • Survival Rate
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MIRN19 microRNA, human
  • MicroRNAs