title: miR-155 expression and correlation with clinical outcome in pediatric AML: A report from Children's Oncology Group.
abstract: Aberrant expression of microRNA-155 (miR-155) has been implicated in acute myeloid leukemia (AML) and associated with clinical outcome.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors: University of Washington School of Medicine, Seattle, Washington.
authors: Ranjani
authors: R
authors: Ramamurthy
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Seattle Children's Hospital, Seattle, Washington.
authors: Maya
authors: M
authors: Hughes
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Valerie
authors: V
authors: Morris
authors: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Hamid
authors: H
authors: Bolouri
authors: Children's Oncology Group, Monrovia, California.
authors: Robert B
authors: RB
authors: Gerbing
authors: Children's Oncology Group, Monrovia, California.
authors: Yi-Cheng
authors: YC
authors: Wang
authors: Hematologics, Inc, Seattle, Washington.
authors: Michael R
authors: MR
authors: Loken
authors: Children's Oncology Group, Monrovia, California.|Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors: Susana C
authors: SC
authors: Raimondi
authors: Children's Oncology Group, Monrovia, California.|Division of Laboratory Medicine, University of Minnesota Medical Center-Fairview, Minneapolis, Minnesota.
authors: Betsy A
authors: BA
authors: Hirsch
authors: Children's Oncology Group, Monrovia, California.|Children's Mercy Hospitals & Clinics, Kansas City, Missiouri.
authors: Alan S
authors: AS
authors: Gamis
authors: University of Washington School of Medicine, Seattle, Washington.|Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Vivian G
authors: VG
authors: Oehler
authors: Keck School of Medical Department of Preventive Medicine, University of Southern California, Los Angeles, California.
authors: Todd A
authors: TA
authors: Alonzo
authors: University of Washington School of Medicine, Seattle, Washington. smeshinc@fhcrc.org.|Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. smeshinc@fhcrc.org.|Seattle Children's Hospital, Seattle, Washington. smeshinc@fhcrc.org.|Children's Oncology Group, Monrovia, California. smeshinc@fhcrc.org.
authors: Soheil
authors: S
authors: Meshinchi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: AML; children; miR-155