Blocking the Proliferation of B-cells in Leukemia

Chronic Lymphocytic Leukemia (CLL) is a malignant disease caused by uncontrolled proliferation of B-cells, a type of white blood cells. The high proliferation rate is due to blockage of the cells’ self destruction mechanism called apoptosis, which allows the cells to multiply in high levels. A group of scientists from Israel and the USA, headed by Professor Idit Shachar from the Weizmann Institute in Israel, found a way to overcome this blockage and allow the B-cells to achieve apoptosis. This new development may allow us to discontinue the proliferation of CLL in the body, and is now pending clinical trials.
Acute Myelogenous Leukemia (Credit: University of Virginia)
Acute Myelogenous Leukemia
(Credit: University of Virginia)

Like other kinds of leukemia, CLL is a cancer in the white blood cells. CLL affects a particular type of white blood cells: B-cells. Normally, the B-cells fight infections, but the cancerous B-cells lose this ability due to DNA mutations. Moreover, the mutations cause these B-cells to proliferate without control and they crowd out the healthy B-cells. The majority of CLL patients are males, and it is considered to be a disease of the elderly since it is rarely encountered in individuals under the age of 40. The disease is treated according to its severity in a specific patient, mainly by chemotherapy. This scientific achievement introduces a new therapeutic pathway.

The research suggests that a receptor protein located on the B-cells’ membrane is responsible for their ‘immortality’ (the subjugation of their apoptosis). The protein, named CD74, was previously found to be more active in CLL B-cells than in normal B-cells. The scientists hypothesized that it regulates the survival of the B-cells and that by having large amounts of it the cells eventually become ‘immortal’. Another fact that supports this hypothesis is that the CD74 needs to bind a small protein in order to activate its “lifesaving” mechanism, and this other protein was also found in high levels in CLL B-cells. The scientists assumed that blocking the binding of these two proteins will prevent them from activating the anti-apoptotic mechanism.

Using antibodies to disable the receptor protein CD74 from binding with the other protein, the scientists achieved a soaring mortality rate of CLL B-cells. The antibodies used in the experiment are produced by the New Jersey based Immunomedics company. Up to now, the antibodies were being tested against several types of leukemia without a full understanding of the mechanism. Now that the mechanism is known, clinical trials for CLL are being planned by Immunomedics. According to Professor Shachar: “Blocking the receptor or other stages in the pathway they activate might be a winning tactic, in the future, in the war against cancers involving B cells.”

More information can be found on the Weizmann Institute website.