2. Core binding factor acute myeloid leukemia

Rearrangements of genetic material affecting the CBFB gene are involved in a form of blood cancer known as acute myeloid leukemia (AML). Because the genetic changes affect CBF, the condition is classified as core binding factor AML (CBF-AML). The most common of these rearrangements is an inversion of a region of chromosome 16 (written as inv(16)). An inversion involves breakage of the chromosome in two places; the resulting piece of DNA is reversed and reinserted into the chromosome. Less commonly, a rearrangement known as a translocation occurs between the two copies of chromosome 16 (written as t(16;16)). In this translocation, pieces of DNA from each copy of the chromosome break off and are interchanged. Both types of genetic rearrangement lead to the fusion of parts of two genes on chromosome 16, CBFB and MYH11. These rearrangements are associated with 5 to 8 percent of cases of AML in adults.

When these rearrangements occur in early blood cells, the function of the RUNX1 protein is particularly affected. The protein produced from the fusion gene, called CBFβ-MYH11, can still bind to RUNX1 to form CBF. However, the function of CBF is impaired. The presence of CBFβ-MYH11 may block binding of CBF to DNA, preventing RUNX1 from controlling gene activity. Alternatively, the MYH11 portion of the fusion protein may interact with other proteins that prevent RUNX1 from controlling gene activity. This change in gene activity blocks the maturation (differentiation) of blood cells and leads to the production of abnormal, immature white blood cells called myeloid blasts. While inv(16) and t(16;16) are important for leukemia development, one or more additional genetic changes are typically needed for the myeloid blasts to develop into cancerous leukemia cells.