Mutations of CEBPA in acute myeloid leukemia FAB types M1 and M2

CEBPA encodes the transcription factor C/EBPα and is specifically up‐regulated during granulocytic differentiation. The gene is mutated in approximately 20% of patients with acute myeloid leukemia (AML) FAB type M2 and occurs in the absence of the t(8;21). In much the same way as specific translocat...

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Bibliographic Details
Published in:Genes chromosomes & cancer 2003-05, Vol.37 (1), p.72-78
Main Authors: Snaddon, Jennifer, Smith, Matthew L., Neat, Michael, Cambal-Parrales, Maxine, Dixon-McIver, Amanda, Arch, Rachael, Amess, John A., Rohatiner, Ama Z., Lister, T. Andrew, Fitzgibbon, Jude
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Amino Acid Sequence - genetics
CCAAT-Enhancer-Binding Protein-alpha - genetics
DNA Mutational Analysis
DNA, Neoplasm - genetics
Female
Humans
Leucine Zippers - genetics
Leukemia, Myeloid, Acute - classification
Leukemia, Myeloid, Acute - genetics
Male
Middle Aged
Molecular Sequence Data
Mutation - genetics
Risk Factors
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Summary:CEBPA encodes the transcription factor C/EBPα and is specifically up‐regulated during granulocytic differentiation. The gene is mutated in approximately 20% of patients with acute myeloid leukemia (AML) FAB type M2 and occurs in the absence of the t(8;21). In much the same way as specific translocations are associated with a particular AML FAB type, the identification of non‐random associations of gene mutation with karyotype or FAB type may be helpful in elucidating the molecular basis of certain forms of leukemia. To confirm these initial findings, 99 patients with AML FAB type M1 or M2 were screened for CEBPA mutations by use of a PCR–single‐strand conformational polymorphism and sequencing approach. Nine CEBPA mutations were identified in eight patients. The mutations were clustered toward the COOH terminal of the protein and occurred exclusively in the intermediate cytogenetic risk group (8/64, 12.5%). Two patients with biallelic mutation, one homozygous for 1137Ins (57 bp) and another with two CEBPA mutations, 1096Ins (27 bp) and 363Ins (GGCC), were observed. There was no evidence for deletion of this region in the other six mutated samples analyzed by fluorescence in situ hybridization with a BAC clone spanning the CEBPA locus. CEBPA mutation status was not demonstrated to be of prognostic importance in this patient group, although this may reflect the selection and size of the AML population studied. In conclusion, mutation of CEBPA is a recurrent finding in AML and appears specific to the intermediate cytogenetic risk group patients. © 2003 Wiley‐Liss, Inc.
ISSN:1045-2257
1098-2264
DOI:10.1002/gcc.10185