CEBPA

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. It is believed to act as a tumor suppressor, which means that it is involved in cellular mechanisms that help to prevent the cells from growing and dividing too rapidly or in an uncontrolled way.

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 a blood cancer called familial acute myeloid leukemia with mutated CEBPA. 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. The effect of this second mutation on the development of acute myeloid leukemia is unclear.

other cancers - associated with the CEBPA gene

Somatic CEBPA gene mutations have also been identified in the leukemia cells of some people with non-familial (sporadic) acute myeloid leukemia. The CEBPA gene mutations identified in the leukemia cells of people with sporadic acute myeloid leukemia generally inhibit 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, allowing 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 acute myeloid leukemia.