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Title: Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
Authors: Akasaka, Takashi ×
Balasas, Theodore
Russell, Lisa J
Sugimoto, Kei-ji
Majid, Aneela
Walewska, Renata
Karran, E Loraine
Brown, David G
Cain, Kelvin
Harder, Lana
Gesk, Stefan
Martin-Subero, Jose Ignacio
Atherton, Mark G
Brüggemann, Monika
Calasanz, María José
Davies, Teresa
Haas, Oskar A
Hagemeijer-Hausman, Anne
Kempski, Helena
Lessard, Michel
Lillington, Debra M
Moore, Sarah
Nguyen-Khac, Florence
Radford-Weiss, Isabelle
Schoch, Claudia
Struski, Stéphanie
Talley, Polly
Welham, Melanie J
Worley, Helen
Strefford, Jon C
Harrison, Christine J
Siebert, Reiner
Dyer, Martin J S #
Issue Date: Apr-2007
Publisher: W.B. Saunders
Series Title: Blood vol:109 issue:8 pages:3451-61
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.
URI: 
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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