title: RUNX1 Amplification Increases the Risk for Thrombosis in Children With B-cell Acute Lymphoblastic Leukemia.
abstract: BACKGROUND
  RUNX1 (AML1) amplification in patients with B-cell acute lymphoblastic leukemia (B-ALL) has been associated with poor survival for unclear reasons. Our anecdotal experience suggests that children with B-ALL and RUNX1 amplification might be predisposed to thrombosis.
  
  
  METHODS
  We performed a retrospective cohort study of children with B-ALL treated from 2008 to 2014 at the North Carolina Children's Hospital. Patient demographics, cytogenetics, and diagnosis of thrombosis were extracted by blinded chart review. Analysis was performed examining the relationship between RUNX1 amplification and thrombosis.
  
  
  RESULTS
  We identified 119 patients with B-ALL and a median age of 4.9 years (interquartile range, 2.9 to 8.6 y) at diagnosis. Four patients (3%) had RUNX1 amplification. The average number of RUNX1 copies among those with amplification was 5 (SD 0.81 [range, 4 to 6]). Eighteen thromboses were diagnosed within 6 months of starting treatment. These events were more likely among patients with RUNX1 amplification than in patients without amplification (75% vs. 13%; RR 5.75, 95% confidence interval, 2.75-12.01).
  
  
  CONCLUSIONS
  RUNX1 amplification may predispose to early thrombotic events in children with B-ALL which could, in part, contribute to their poorer outcomes. Treatment implications, including possible prophylactic anticoagulation of patients with of RUNX1 amplification, justify larger studies to confirm these findings.
authors.affiliation: *The Division of Pediatric Hematology & Oncology †The University of North Carolina Lineberger Comprehensive Cancer Center ‡The Department of Pediatrics §The Department of Pathology & Laboratory Medicine ∥The Biostatistics and Clinical Data Management Core, University of North Carolina Lineberger Comprehensive Cancer Center, the University of North Carolina School of Medicine, Chapel Hill, NC.
authors.forename: Maria O
authors.initials: MO
authors.lastname: Boucher
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Smitherman
authors.forename: Kristy S
authors.initials: KS
authors.lastname: Pahl
authors.forename: Kathleen W
authors.initials: KW
authors.lastname: Rao
authors.forename: Allison M
authors.initials: AM
authors.lastname: Deal
authors.forename: Julie
authors.initials: J
authors.lastname: Blatt
mesh_terms: D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000235:genetics*; D012189:Retrospective Studies; D013927:Thrombosis / Q000235:genetics*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human