title: Pediatric B-lymphoblastic leukemia with RUNX1 amplification: clinicopathologic study of eight cases.
abstract: B-lymphoblastic leukemia (a.k.a. precursor B-cell acute lymphoblastic leukemia) is a heterogeneous disease at the clinical, morphologic, immunophenotypic and genetic levels. Recurrent genetic abnormalities in B-lymphoblastic leukemia with prognostic significance are well known and specifically delineated in the WHO 2008 classification (eg hyperdiploidy, t(9;22)(q34;q11.2); BCR-ABL1, t(12;21)(p13;q22); ETV6-RUNX1). In recent years, a subgroup of B-lymphoblastic leukemia with the recurring genetic alteration of RUNX1 amplification has emerged. This subgroup has a low incidence (2%) and an increased risk of relapse and overall worse outcome. Given these apparently distinctive clinicopathologic features, we evaluated eight cases of pediatric B-lymphoblastic leukemia with RUNX1 amplification treated on Children's Oncology Group protocols from 2000-2009. Compared with 25 consecutive B-lymphoblastic leukemia cases without RUNX1 amplification, we identified a trend toward male predominance (P-value=0.082) and low white blood cell count at presentation (P-value=0.081) in B-lymphoblastic leukemia with RUNX1 amplification. Older age at presentation was significant (median age 9.5 years, P-value=0.006). There was no significant difference in the presence of central nervous system disease, CD20 or myeloid antigen positivity on the blasts or percent circulating blasts in B-lymphoblastic leukemia with RUNX1 amplification versus other B-lymphoblastic leukemia types. Seven of eight patients (88%) are alive and free of disease at the time of last checkup (mean 50 months, range 14-116 months). Although we see a relatively good outcome in our small cohort of patients, recent findings from the Children's Oncology Group on a large set of patients suggests otherwise that these patients may have an inferior outcome compared with patients with B-lymphoblastic leukemia without RUNX1 amplification. Long-term follow-up in larger cohorts including minimal residual disease correlation is required.
authors.affiliation: Department of Pathology, University of New Mexico, Health Sciences Center, Albuquerque, NM, USA. kreichard@salud.unm.edu
authors.forename: Kaaren K
authors.initials: KK
authors.lastname: Reichard
authors.forename: Huining
authors.initials: H
authors.lastname: Kang
authors.forename: Sheldon
authors.initials: S
authors.lastname: Robinett
mesh_terms: D000293:Adolescent; D000367:Age Factors; D014408:Biomarkers, Tumor / Q000032:analysis; D002648:Child; 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; D007621:Karyotyping; D008297:Male; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human