Upregulation of the EMT marker vimentin is associated with poor clinical outcome in acute myeloid leukemia

J Transl Med. 2018 Jun 20;16(1):170. doi: 10.1186/s12967-018-1539-y.

Abstract

Background: Vimentin (VIM) is a type III intermediate filament that maintains cell integrity, and is involved in cell migration, motility and adhesion. When overexpressed in solid cancers, vimentin drives epithelial to mesenchymal transition (EMT) and ultimately, metastasis. The effects of its overexpression in AML are unclear.

Methods: In this study, we analyzed the TCGA data of 173 AML patients for which complete clinical and expression data were available. In this analysis, we assessed the association between VIM mRNA expression and patient's clinical and molecular characteristics including clinical outcome.

Results: VIM overexpression was associated with higher white blood count (< p = 0.0001). Patients with high VIM expression have worse overall survival (OS) and disease-free survival (DFS) compared with patients with low VIM expression (median OS; 7.95 months vs 19.2 months; p = 0.029). After age-stratification, high VIM expression was significantly associated with worse overall survival in older patients (age ≥ 60; median OS: 5.4 vs 9.9 months: p = 0.0257) but not in younger patients (age < 60). In stratification analysis according to cytogenetic status, high VIM expression was significantly associated with shorter OS (7.95 vs 24.6 months: p = 0.0102) in cytogenetically normal, but not in cytogenetic abnormal AML.

Conclusions: Collectively, the data indicate that overexpression of the EMT marker vimentin is associated with poor clinical outcome in older patients with cytogenetically normal AML; and therefore may play a role in this disease.

Keywords: AML; EMT; Overall survival; Vimentin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology*
  • Male
  • Methylation
  • Middle Aged
  • Multivariate Analysis
  • Mutation / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Treatment Outcome
  • Up-Regulation / genetics*
  • Vimentin / genetics*
  • Vimentin / metabolism
  • Young Adult

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • Vimentin