Acute myeloid leukemia factor nuclear binding (Core binding factor acute myeloid leukemia) - Genes RUNX1, runx1t1, CBFB, and MYH11.

Acute myeloid leukemia factor nuclear binding (CBF-LMA) is a form of neoplasia marrow called acute myelogenous leukemia. 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 CBF-AML 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 easy bruising and abnormal bleeding. Other symptoms of the disease may include fever and weight loss. While acute myeloid leukemia is a disease that usually manifests itself in late adulthood, CBF-AML often begins in adulthood and can occur in childhood. Compared to other forms of acute myeloid leukemia, CBF-AML has a relatively good prognosis: about 90% of individuals with CBF-AML recovering from his illness after treatment, compared with between 25% to 40% those with other forms of acute myeloid leukemia. However, the disease recurs in about half of cases after treatment of initial appearance.

This disease is related to chromosomal rearrangements between chromosomes 8 and 21, and chromosome rearrangements 16. RUNX1 involve genes, runx1t1, CBFB and MYH11. Two of these genes, the RUNX1 gene, located on the long arm of chromosome 21 (21q22.3) and CBFB gene, located on the long arm of chromosome 16 (16q22.1), encoding two pieces (CBF? and RUNX1) of a protein complex known as core binding factor (CBF). This protein complex binds to specific regions of DNA and helps to activate specific genes. In particular, plays an important role in the development of hematopoietic stem cells. Chromosomal rearrangements involving the RUNX1 gene or gene CBFB alter CBF, leading to leukemia.

In CBF-AML, the RUNX1 gene is affected by a type of genetic rearrangement known as a translocation. In this exchange, two pieces of DNA chromosomes are excised and exchanged. The most common translocation, called t (8; 21), fuses a part of the RUNX1 gene on chromosome 21 with part of runx1t1 gene (also known as ETO), located on the long arm of chromosome 8 (8q22), in chromosome 8. the combination of these genes leads to encoding the fusion protein RUNX1-ETO. This fusion protein is capable of forming CBF and attached to DNA, like the normal protein RUNX1. However, because the function of the encoded protein from the normal gene is runx1t1 block the activity of the gene, abnormal CBF genes turns off rather than turn them.

Other genetic rearrangements associated with disease CBFB alter gene. The most common of these rearrangements is a reversal of a region of chromosome 16 (inv (16). An inversion involves cleavage of chromosome in two places. The piece resulting DNA is inverted and reinserted into the chromosome. The investment inv (16) leads to the fusion of two genes on chromosome 16, the CBFB gene and the gene MYH11, located on the short arm of chromosome 16 (16p13.11). less often a translocation involving chromosome 16, ( t (16; 16), leading to the fusion of two genes encoded protein from these genetic rearrangements called CBF?-MYH11 fusion protein may form CBF, but it is believed that the presence of the portion MYH11.. of the fusion protein prevents binding to DNA CBF, affecting its ability to control gene activity. Alternatively, MYH11 part can interact with other proteins that prevent CBF control gene activity.

The change in gene activity caused by the alteration of CBF blocks the differentiation of blood cells and leads to the production mieloblastoides cells. However, one or more genetic changes must occur for the mieloblastoides cells become neoplastic leukemia cells.

Acute myeloid leukemia factor nuclear binding but not inherited genetic rearrangements arises from occurring in the body cells after conception.

Tests performed in IVAMI: in IVAMI perform the detection of mutations associated with acute myeloid leukemia factor nuclear binding (CBF-MAL), by complete PCR amplification of the exons of the RUNX1, runx1t1, CBFB and MYH11 genes, respectively, 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).