Pathophysiology of hairy cell leukemia
The abnormalities found in patients with hairy cell leukemia are due to changes in B-cell lymphocytes. The replication of these white blood cells becomes excessive, and the aberrant cells start infiltrating in the bone marrow, causing alterations. Infiltration occurs because the abnormal cells express a receptor that interacts with the vascular adhesion molecule 1, which can be found in the bone marrow, the liver, spleen, and other structures. In the majority of cases, this infiltration causes pancytopenia, which means a reduction of all types of functioning cells in the blood. Other sites of infiltration include the spleen and the liver, which is why these patients have enlarged abdominal organs, too. Lymph nodes are not usually involved or infiltrated by aberrant cells, which is a key feature of hairy cell leukemia.
The genetic cause of hairy cell leukemia is through the abnormal activation of a signaling pathway called RAF-MEK-ERK. This pathway becomes activated through a mutation called BRAF-V600E, which has been characterized and can be detected in genetic studies. As a result of this mutation, B-cells stop undergoing apoptosis (programmed cellular death), adopt a hairy pattern, and replicates excessively.
Another genetic abnormality usually found in hairy cell leukemia is the overexpression of a protein called cyclin D1. This protein is a regulator of the cell cycle and may be involved in the abnormal replication of B cells found in this type of leukemia.
The cause of such genetic change is not yet clear, but exposure to certain types of substances might be involved. Organophosphorus insecticides and exposure to benzene have been proposed as possible risk factors, but this is only a hypothesis. Exposure to radiation and previous infections with mononucleosis may also play an important role.