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Genetics Home Reference: your guide to understanding genetic conditions
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CEBPA

Reviewed January 2014

What is the official name of the CEBPA gene?

The official name of this gene is “CCAAT/enhancer binding protein (C/EBP), alpha.”

CEBPA is the gene's official symbol. The CEBPA gene is also known by other names, listed below.

What is the normal function of the CEBPA gene?

The CEBPA gene provides instructions for making a protein called CCAAT/enhancer-binding protein alpha. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity (expression) of certain genes. CCAAT/enhancer-binding protein alpha is involved in the maturation (differentiation) of certain blood cells. It is also believed to act as a tumor suppressor, which means that it is involved in cellular mechanisms that help prevent the cells from growing and dividing too rapidly or in an uncontrolled way.

Does the CEBPA gene share characteristics with other genes?

The CEBPA gene belongs to a family of genes called bZIP (basic leucine zipper proteins).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the CEBPA gene related to health conditions?

familial acute myeloid leukemia with mutated CEBPA - caused by mutations in the CEBPA gene

At least six mutations in the CEBPA gene have been identified in families with familial acute myeloid leukemia with mutated CEBPA, which is a form of a blood cancer known as acute myeloid leukemia. These inherited mutations are present throughout a person's life in virtually every cell in the body. The mutations result in a shorter version of CCAAT/enhancer-binding protein alpha. This shortened protein is produced from one copy of the CEBPA gene in each cell, and it is believed to interfere with the tumor suppressor function of the normal protein produced from the second copy of the gene. Absence of the tumor suppressor function of CCAAT/enhancer-binding protein alpha is believed to disrupt the regulation of blood cell production, leading to the uncontrolled production of abnormal cells that occurs in acute myeloid leukemia.

In addition to the inherited mutation in one copy of the CEBPA gene in each cell, most individuals with familial acute myeloid leukemia with mutated CEBPA also acquire a mutation in the second copy of the CEBPA gene. The additional mutation, which is called a somatic mutation, is found only in the cancerous leukemia cells and is not inherited. The somatic CEBPA gene mutations that have been identified in leukemia cells generally decrease the DNA-binding ability of CCAAT/enhancer-binding protein alpha. Researchers suggest that this second mutation may affect the normal differentiation of blood cells, although exactly how the mutation is involved in the development of acute myeloid leukemia is unclear.

cytogenetically normal acute myeloid leukemia - associated with the CEBPA gene

Mutations in the CEBPA gene have been identified in some people with a form of acute myeloid leukemia known as cytogenetically normal acute myeloid leukemia (CN-AML). While large chromosomal abnormalities can be involved in the development of acute myeloid leukemia, about half of cases do not have these abnormalities; these are classified as CN-AML. Mutations in this gene are found in approximately 18 percent of individuals with CN-AML. When associated with CEBPA gene mutations, this condition can be inherited, in which case it is called familial acute myeloid leukemia with mutated CEBPA (described above), or not inherited (sporadic acute myeloid leukemia with mutated CEBPA).

Two types of CEBPA gene mutations can occur in both the inherited and non-inherited forms of CN-AML. One type leads to production of an abnormally short protein that interferes with the tumor suppressor function of normal versions of CCAAT/enhancer-binding protein alpha. The other type of mutation blocks the DNA-binding ability of CCAAT/enhancer-binding protein alpha. Impaired DNA binding interferes with the protein's ability to regulate gene expression and impairs its tumor suppressor function. Impairment of the tumor suppressor function of CCAAT/enhancer-binding protein alpha leads to the uncontrolled production of abnormal white blood cells that occurs in acute myeloid leukemia.

Between 50 and 75 percent of all individuals who have acute myeloid leukemia with mutations in the CEBPA gene, both sporadic and familial, have two mutated CEBPA genes in each leukemia cell. The rest have only one CEBPA gene mutation. In the sporadic cases the mutation appears only in the leukemia cells, and in the familial cases it is present throughout the body. Somatic mutations in other genes can also contribute to the development of CN-AML.

Where is the CEBPA gene located?

Cytogenetic Location: 19q13.1

Molecular Location on chromosome 19: base pairs 33,299,933 to 33,302,563

The CEBPA gene is located on the long (q) arm of chromosome 19 at position 13.1.

The CEBPA gene is located on the long (q) arm of chromosome 19 at position 13.1.

More precisely, the CEBPA gene is located from base pair 33,299,933 to base pair 33,302,563 on chromosome 19.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about CEBPA?

You and your healthcare professional may find the following resources about CEBPA helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the CEBPA gene or gene products?

  • CCAAT/enhancer-binding protein alpha
  • CEBP
  • CEBPA_HUMAN
  • C/EBP-alpha
  • c/EBP alpha

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding CEBPA?

acute ; acute myeloid leukemia ; AML ; cancer ; cell ; differentiation ; DNA ; enhancer ; familial ; gene ; gene expression ; inherited ; leukemia ; mutation ; myeloid ; protein ; somatic mutation ; sporadic ; transcription ; transcription factor ; tumor ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Carmichael CL, Wilkins EJ, Bengtsson H, Horwitz MS, Speed TP, Vincent PC, Young G, Hahn CN, Escher R, Scott HS. Poor prognosis in familial acute myeloid leukaemia with combined biallelic CEBPA mutations and downstream events affecting the ATM, FLT3 and CDX2 genes. Br J Haematol. 2010 Aug;150(3):382-5. doi: 10.1111/j.1365-2141.2010.08204.x. Epub 2010 Apr 29. (http://www.ncbi.nlm.nih.gov/pubmed/20456351?dopt=Abstract)
  • OMIM: CCAAT/ENHANCER-BINDING PROTEIN, ALPHA (http://omim.org/entry/116897)
  • Nanri T, Uike N, Kawakita T, Iwanaga E, Mitsuya H, Asou N. A family harboring a germ-line N-terminal C/EBPalpha mutation and development of acute myeloid leukemia with an additional somatic C-terminal C/EBPalpha mutation. Genes Chromosomes Cancer. 2010 Mar;49(3):237-41. doi: 10.1002/gcc.20734. (http://www.ncbi.nlm.nih.gov/pubmed/19953636?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1050)
  • Owen C, Barnett M, Fitzgibbon J. Familial myelodysplasia and acute myeloid leukaemia--a review. Br J Haematol. 2008 Jan;140(2):123-32. doi: 10.1111/j.1365-2141.2007.06909.x. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18173751?dopt=Abstract)
  • Pabst T, Eyholzer M, Haefliger S, Schardt J, Mueller BU. Somatic CEBPA mutations are a frequent second event in families with germline CEBPA mutations and familial acute myeloid leukemia. J Clin Oncol. 2008 Nov 1;26(31):5088-93. doi: 10.1200/JCO.2008.16.5563. Epub 2008 Sep 2. (http://www.ncbi.nlm.nih.gov/pubmed/18768433?dopt=Abstract)
  • Pabst T, Mueller BU, Zhang P, Radomska HS, Narravula S, Schnittger S, Behre G, Hiddemann W, Tenen DG. Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPalpha), in acute myeloid leukemia. Nat Genet. 2001 Mar;27(3):263-70. (http://www.ncbi.nlm.nih.gov/pubmed/11242107?dopt=Abstract)
  • Pabst T, Mueller BU. Complexity of CEBPA dysregulation in human acute myeloid leukemia. Clin Cancer Res. 2009 Sep 1;15(17):5303-7. doi: 10.1158/1078-0432.CCR-08-2941. Epub 2009 Aug 25. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19706798?dopt=Abstract)
  • Quintana-Bustamante O, Lan-Lan Smith S, Griessinger E, Reyal Y, Vargaftig J, Lister TA, Fitzgibbon J, Bonnet D. Overexpression of wild-type or mutants forms of CEBPA alter normal human hematopoiesis. Leukemia. 2012 Jul;26(7):1537-46. doi: 10.1038/leu.2012.38. Epub 2012 Feb 10. (http://www.ncbi.nlm.nih.gov/pubmed/22371011?dopt=Abstract)
  • Renneville A, Mialou V, Philippe N, Kagialis-Girard S, Biggio V, Zabot MT, Thomas X, Bertrand Y, Preudhomme C. Another pedigree with familial acute myeloid leukemia and germline CEBPA mutation. Leukemia. 2009 Apr;23(4):804-6. doi: 10.1038/leu.2008.294. Epub 2008 Oct 23. (http://www.ncbi.nlm.nih.gov/pubmed/18946494?dopt=Abstract)
  • Smith ML, Cavenagh JD, Lister TA, Fitzgibbon J. Mutation of CEBPA in familial acute myeloid leukemia. N Engl J Med. 2004 Dec 2;351(23):2403-7. (http://www.ncbi.nlm.nih.gov/pubmed/15575056?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2014
Published: November 24, 2014