Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL)

Takashi Akasaka(University of Leicester), Theodore Balasas(University of Leicester), Lisa J. Russell(Blood Cancer UK), Keiji Sugimoto(University of Leicester), Aneela Majid(University of Leicester), Renata Walewska(University of Leicester), E. Loraine Karran(University of Leicester), David G. Brown(University of Leicester), Kelvin Cain(University of Leicester), Lana Harder(University Hospital Schleswig-Holstein), Stefan Gesk(University Hospital Schleswig-Holstein), José I. Martín‐Subero(University Hospital Schleswig-Holstein), Mark Atherton(University of Liverpool), Monika Brüggemann(University Hospital Schleswig-Holstein), Marı́a José Calasanz(Universidad de Navarra), Teresa Davies(Southmead Hospital), Oskar A. Haas(St Anna Children's Hospital), Anne Hagemeijer, Helena Kempski(Great Ormond Street Hospital), Michel Lessard(Hôpital d'Hautepierre), Debra M. Lillington(St Bartholomew's Hospital), Sarah Moore(South Australia Pathology), Florence Nguyen‐Khac(Inserm), Isabelle Radford‐Weiss(Hôpital Necker-Enfants Malades), Claudia Schoch(Munich Leukemia Laboratory (Germany)), Stéphanie Struski(Hôpital d'Hautepierre), Polly Talley(Sheffield Children's Hospital), Melanie J. Welham(University of Bath), Helen Worley(Blood Cancer UK), Jonathan C. Strefford(Blood Cancer UK), Christine J. Harrison(Blood Cancer UK), Reiner Siebert(University Hospital Schleswig-Holstein), Martin J.S. Dyer(University of Leicester)
Blood
December 14, 2006
10.1182/blood-2006-08-041012
Cited by 212

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.

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