title: Heterogeneity of Abnormal RUNX1 Leading to Clinicopathologic Variations in Childhood B-Lymphoblastic Leukemia.
abstract: OBJECTIVE
  Abnormalities of the RUNX1 gene in childhood B-acute lymphoblastic leukemia (B-ALL) are manifested by ETV6-RUNX1 or RUNX1 amplification. A detailed comparison between the two regarding clinicopathologic features with genetic analysis has not been performed previously. This parallel study assessed how different RUNX1 abnormalities affect the clinicopathology of B-ALL.
  
  
  METHODS
  We compared clinicopathologic factors, including age, sex, WBC count, cerebrospinal fluid (CSF) involvement, immunophenotype, and blast proliferation rate between B-ALL with RUNX1 amplification (10 cases) and B-ALL with ETV6-RUNX1 translocation (67 cases) in childhood B-ALL.
  
  
  RESULTS
  CD7 was often expressed in RUNX1 amplification but not in ETV6-RUNX1 (44% vs 0%, P = .0001) and appeared to correlate with CSF involvement in the former group (3/4 [75%]). CD13 was often detected in ETV6-RUNX1 with additional RUNX1 gain (38%) with an even higher frequency in double ETV6-RUNX1 translocation (77%), but was not detected in RUNX1 amplification (0%, P < .05). Children with RUNX1 amplification were older and more often CSF positive, while those with ETV6-RUNX1 were younger, more frequently had hyperleukocytosis, and had higher blast proliferation rates.
  
  
  CONCLUSIONS
  RUNX1 copy numbers seem to be proportional to the age of B-ALL onset and the frequency of CSF involvement, while RUNX1 amplification vs translocation causes aberrant expression of CD7 and CD13, respectively.
authors.affiliation: From the Department of Pathology and.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Knez
authors.affiliation: From the Department of Pathology and Colorado Genetics Laboratory, University of Colorado School of Medicine, Aurora and.
authors.forename: Billie J
authors.initials: BJ
authors.lastname: Carstens
authors.affiliation: From the Department of Pathology and Colorado Genetics Laboratory, University of Colorado School of Medicine, Aurora and.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Swisshelm
authors.affiliation: Department of Pathology, Children's Hospital Colorado, Aurora.
authors.forename: Amy N
authors.initials: AN
authors.lastname: McGranahan
authors.affiliation: From the Department of Pathology and Department of Pathology, Children's Hospital Colorado, Aurora. liang.xiayuan@childrenscolorado.org.
authors.forename: Xiayuan
authors.initials: X
authors.lastname: Liang
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000818:Animals; D019011:Antigens, CD7 / Q000096:biosynthesis / Q000276:immunology; D018826:CD13 Antigens / Q000096:biosynthesis / Q000276:immunology; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D005784:Gene Amplification; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology*; D011817:Rabbits; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D019011:Antigens, CD7; D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human; D018826:CD13 Antigens
keywords: Acute lymphoblastic leukemia; ETV6-RUNX1; Precursor B-lymphoblastic leukemia; RUNX1; TEL-AML1; iAMP21