title: Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
abstract: CCAAT enhancer-binding protein (CEBP) transcription factors play pivotal roles in proliferation and differentiation, including suppression of myeloid leukemogenesis. Mutations of CEBPA are found in a subset of acute myeloid leukemia (AML) and in some cases of familial AML. Here, using cytogenetics, fluorescence in situ hybridization (FISH), and molecular cloning, we show that 5 CEBP gene family members are targeted by recurrent IGH chromosomal translocations in BCP-ALL. Ten patients with t(8;14)(q11;q32) involved CEBPD on chromosome 8, and 9 patients with t(14;19)(q32;q13) involved CEBPA, while a further patient involved CEBPG, located 71 kb telomeric of CEBPA in chromosome band 19q13; 4 patients with inv(14)(q11q32)/t(14;14)(q11;q32) involved CEBPE and 3 patients with t(14;20)(q32;q13) involved CEBPB. In 16 patients the translocation breakpoints were cloned using long-distance inverse-polymerase chain reaction (LDI-PCR). With the exception of CEBPD breakpoints, which were scattered within a 43-kb region centromeric of CEBPD, translocation breakpoints were clustered immediately 5' or 3' of the involved CEBP gene. Except in 1 patient with t(14;14)(q11;q32), the involved CEBP genes retained germ-line sequences. Quantitative reverse transcription (RT)-PCR showed overexpression of the translocated CEBP gene. Our findings implicate the CEBP gene family as novel oncogenes in BCP-ALL, and suggest opposing functions of CEBP dysregulation in myeloid and lymphoid leukemogenesis.
authors.affiliation: Toxicology Unit, Medical Research Council, University of Leicester, Lancaster Road, Leicester, UK.
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasaka
authors.forename: Theodore
authors.initials: T
authors.lastname: Balasas
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Russell
authors.forename: Kei-ji
authors.initials: KJ
authors.lastname: Sugimoto
authors.forename: Aneela
authors.initials: A
authors.lastname: Majid
authors.forename: Renata
authors.initials: R
authors.lastname: Walewska
authors.forename: E Loraine
authors.initials: EL
authors.lastname: Karran
authors.forename: David G
authors.initials: DG
authors.lastname: Brown
authors.forename: Kelvin
authors.initials: K
authors.lastname: Cain
authors.forename: Lana
authors.initials: L
authors.lastname: Harder
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Martin-Subero
authors.forename: Mark G
authors.initials: MG
authors.lastname: Atherton
authors.forename: Monika
authors.initials: M
authors.lastname: Brüggemann
authors.forename: María José
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: Teresa
authors.initials: T
authors.lastname: Davies
authors.forename: Oskar A
authors.initials: OA
authors.lastname: Haas
authors.forename: Anne
authors.initials: A
authors.lastname: Hagemeijer
authors.forename: Helena
authors.initials: H
authors.lastname: Kempski
authors.forename: Michel
authors.initials: M
authors.lastname: Lessard
authors.forename: Debra M
authors.initials: DM
authors.lastname: Lillington
authors.forename: Sarah
authors.initials: S
authors.lastname: Moore
authors.forename: Florence
authors.initials: F
authors.lastname: Nguyen-Khac
authors.forename: Isabelle
authors.initials: I
authors.lastname: Radford-Weiss
authors.forename: Claudia
authors.initials: C
authors.lastname: Schoch
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Struski
authors.forename: Polly
authors.initials: P
authors.lastname: Talley
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Welham
authors.forename: Helen
authors.initials: H
authors.lastname: Worley
authors.forename: Jon C
authors.initials: JC
authors.lastname: Strefford
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
mesh_terms: D002051:Burkitt Lymphoma / Q000235:genetics*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D002503:Centromere / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D005810:Multigene Family / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016615:Telomere / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D007143:Immunoglobulin Heavy Chains