miR-155 expression and correlation with clinical outcome in pediatric AML: A report from Children's Oncology Group

Ranjani Ramamurthy, Maya Hughes, Valerie Morris, Hamid Bolouri, Robert B. Gerbing, Yi Cheng Wang, Michael R. Loken, Susana C. Raimondi, Betsy A. Hirsch, Alan S. Gamis, Vivian G. Oehler, Todd A. Alonzo, Soheil Meshinchi

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: Aberrant expression of microRNA-155 (miR-155) has been implicated in acute myeloid leukemia (AML) and associated with clinical outcome. Procedure: We evaluated miR-155 expression in 198 children with normal karyotype AML (NK-AML) enrolled in Children's Oncology Group (COG) AML trial AAML0531 and correlated miR-155 expression levels with disease characteristics and clinical outcome. Patients were divided into quartiles (Q1–Q4) based on miR-155 expression level, and disease characteristics were then evaluated and correlated with miR-155 expression. Results: MiR-155 expression varied over 4-log10-fold range relative to its expression in normal marrow with a median expression level of 0.825 (range 0.043–25.630) for the entire study cohort. Increasing miR-155 expression was highly associated with the presence of FLT3/ITD mutations (P < 0.001) and high-risk disease (P < 0.001) and inversely associated with standard-risk (P = 0.008) and low-risk disease (P = 0.041). Patients with highest miR-155 expression had a complete remission (CR) rate of 46% compared with 82% in low expressers (P < 0.001) with a correspondingly lower event-free (EFS) and overall survival (OS) (P < 0.001 and P = 0.002, respectively). In a multivariate model that included molecular risk factors, high miR-155 expression remained a significant independent predictor of OS (P = 0.022) and EFS (0.019). Conclusions: High miR-155 expression is an adverse prognostic factor in pediatric NK-AML patients. Specifically, high miR-155 expression not only correlates with FLT3/ITD mutation status and high-risk disease but it is also an independent predictor of worse EFS and OS.

Original languageEnglish (US)
Pages (from-to)2096-2103
Number of pages8
JournalPediatric Blood and Cancer
Volume63
Issue number12
DOIs
StatePublished - Dec 1 2016

Keywords

  • AML
  • children
  • miR-155

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