What causes chronic lymphocytic leukemia?
Similar to many other types of cancer, chronic lymphocytic leukemia does not have a single cause. It is a multifactorial disease, which means that many different causes interact with each other. There is not an exact cause already identified, but we do know that genetic factors are not as prevalent as in other diseases. It is an acquired disorder, and the majority of cases do not have a familial medical history. In rare familial cases, the median age is reduced from 72 years to 58 years old.
The majority of genes that cause chronic lymphocytic leukemia are proximal to genes that regulate apoptosis. The most common genetic abnormality is a deletion of gene 13q14, and it happens in around half of these patients. When they have this abnormality, their disease progresses very slowly and it is relatively stable. Another abnormality is a trisomy of chromosome 12, which appears in around 15% of patients and 17p13 gene deletions, which compromise the normal function of the p53 tumor suppressor gene. Additionally, it is very common to have an overexpression of a gene called bcl2. This is a proto-oncogene, which means it is a normal gene that triggers cancer when overexpressed.
As a result of a series of genetic alterations in monoclonal cells, patients with chronic lymphocytic leukemia become arrested in the differentiation pathway. The type of cells involved are B-cells, which stays as pre-B cells and do not reach the mature B cell phase. Still, in blood tests, they resemble mature cells very closely, and that’s why they are often counted as such.