PMID- 17170124 OWN - NLM STAT- MEDLINE DCOM- 20070523 LR - 20220129 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 109 IP - 8 DP - 2007 Apr 15 TI - Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). PG - 3451-61 AB - 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. FAU - Akasaka, Takashi AU - Akasaka T AD - Toxicology Unit, Medical Research Council, University of Leicester, Lancaster Road, Leicester, UK. FAU - Balasas, Theodore AU - Balasas T FAU - Russell, Lisa J AU - Russell LJ FAU - Sugimoto, Kei-ji AU - Sugimoto KJ FAU - Majid, Aneela AU - Majid A FAU - Walewska, Renata AU - Walewska R FAU - Karran, E Loraine AU - Karran EL FAU - Brown, David G AU - Brown DG FAU - Cain, Kelvin AU - Cain K FAU - Harder, Lana AU - Harder L FAU - Gesk, Stefan AU - Gesk S FAU - Martin-Subero, Jose Ignacio AU - Martin-Subero JI FAU - Atherton, Mark G AU - Atherton MG FAU - Bruggemann, Monika AU - Bruggemann M FAU - Calasanz, Maria Jose AU - Calasanz MJ FAU - Davies, Teresa AU - Davies T FAU - Haas, Oskar A AU - Haas OA FAU - Hagemeijer, Anne AU - Hagemeijer A FAU - Kempski, Helena AU - Kempski H FAU - Lessard, Michel AU - Lessard M FAU - Lillington, Debra M AU - Lillington DM FAU - Moore, Sarah AU - Moore S FAU - Nguyen-Khac, Florence AU - Nguyen-Khac F FAU - Radford-Weiss, Isabelle AU - Radford-Weiss I FAU - Schoch, Claudia AU - Schoch C FAU - Struski, Stephanie AU - Struski S FAU - Talley, Polly AU - Talley P FAU - Welham, Melanie J AU - Welham MJ FAU - Worley, Helen AU - Worley H FAU - Strefford, Jon C AU - Strefford JC FAU - Harrison, Christine J AU - Harrison CJ FAU - Siebert, Reiner AU - Siebert R FAU - Dyer, Martin J S AU - Dyer MJ LA - eng GR - MC_U132670597/MRC_/Medical Research Council/United Kingdom PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20061214 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (CCAAT-Enhancer-Binding Proteins) RN - 0 (Immunoglobulin Heavy Chains) SB - IM MH - Burkitt Lymphoma/*genetics MH - CCAAT-Enhancer-Binding Proteins/*genetics MH - Centromere/genetics MH - Chromosomes, Human/*genetics MH - Humans MH - Immunoglobulin Heavy Chains/*genetics MH - In Situ Hybridization, Fluorescence MH - Multigene Family/*genetics MH - Oncogenes/*genetics MH - Polymerase Chain Reaction MH - Telomere/genetics MH - *Translocation, Genetic EDAT- 2006/12/16 09:00 MHDA- 2007/05/24 09:00 CRDT- 2006/12/16 09:00 PHST- 2006/12/16 09:00 [pubmed] PHST- 2007/05/24 09:00 [medline] PHST- 2006/12/16 09:00 [entrez] AID - S0006-4971(20)41722-7 [pii] AID - 10.1182/blood-2006-08-041012 [doi] PST - ppublish SO - Blood. 2007 Apr 15;109(8):3451-61. doi: 10.1182/blood-2006-08-041012. Epub 2006 Dec 14.