Acute myeloid leukemia familiar with mutation CEBPA (Familial acute myeloid leukemia With mutated CEBPA) - Gen CEBPA.

Family acute with mutation CEBPA, myeloid leukemia is a form of malignancy of the bone marrow. In normal bone marrow, hematopoietic stem cells develop into various types of blood cells: leukocytes (protect the body from infection), erythrocytes (carry oxygen) and thrombocytes (involved in blood clotting). In acute myelogenous leukemia, bone marrow produces a large number of abnormal white blood cells and immature cells called mieloblastoides. Instead of becoming normal leukocytes, mieloblastoides cells become neoplastic leukemia cells. The large number of abnormal cells in the bone marrow interferes with the production of leukocytes, erythrocytes and thrombocytes functional.

People with familial acute myelogenous leukemia mutation CEBPA have a deficiency of all types of mature blood cells: leucopenia leads to increased susceptibility to infections, anemia causes fatigue and weakness and thrombocytopenia can cause bruising easily and abnormal bleeding. Other symptoms of the disease may include fever and weight loss.

While acute myeloid leukemia is generally a disease of older adults, acute myeloid leukemia familiar with CEBPA mutation manifested often in the early years of life. Between 50% and 65% of affected individuals survive their disease, compared with between 25% and 40% of people with other forms of acute myeloid leukemia. However, people with acute myeloid leukemia familiar with CEBPA mutation have an increased risk of the disease coming back after treatment for the initial appearance.

The gene CEBPA (CCAAT / enhancer binding protein alpha), located on the long arm of chromosome 19 (19q13.1), encodes a protein called transcription factor CCAAT / enhancer binding protein alpha. This protein is involved in the differentiation of certain blood cells. It is also believed that acts as a tumor suppressor.

They have identified at least 6 CEBPA gene mutations in families with familial acute myelogenous leukemia mutation CEBPA. These inherited mutations are present throughout the life of a person in virtually every cell of the body. Mutations leading to a shorter version of CCAAT / enhancer binding protein alpha. It is believed that this shortened protein is encoded from a copy of the gene in every cell CEBPA, and is thought to interfere with the tumor suppressor function of the normal protein encoded from the second gene copy. It is believed that the absence of tumor suppressor function of CCAAT / enhancer binding protein alpha interrupts the regulation of blood cell production, which leads to uncontrolled production of abnormal cells. In addition to the inherited mutation in one copy of the gene in every cell CEBPA, most individuals with the disease also acquire a mutation in CEBPA second copy gene. The additional mutation, called somatic mutation found only in cancer cells and leukemia is not inherited. Somatic mutations of CEBPA genes have been identified in leukemia cells generally decrease DNA binding capacity of CCAAT / enhancer binding protein alpha. It is likely that this second mutation affects the normal differentiation of blood cells, although it is not exactly clear how the mutation is involved in the development of acute myeloid leukemia.

Mutations in CEBPA gene have also been identified in some individuals with a form of acute myelogenous leukemia known as acute myeloid leukemia with normal cytogenetics (CN-AML) - see acute myeloid leukemia with normal cytogenetics (CN-AML), Genes NPM1, FLT3, DNMT3A, CEBPA, IDH1 and IDH2 -.

Family acute myeloid leukemia with CEBPA mutation is inherited as an autosomal dominant pattern. Autosomal dominant inheritance means that a copy of the altered gene in each cell CEBPA is sufficient to express the disease. Most affected individuals also acquire a second somatic mutation, the CEBPA gene in their leukemic cells.

Tests in IVAMI: in IVAMI perform detection of mutations associated with familial acute myeloid leukemia mutation CEBPA, by complete PCR amplification of exons CEBPA gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).