Leukaemia is a cancer that occurs when abnormal blood stem cells (immature white blood cells) are produced in the bone marrow. Normally white cells develop, repair and reproduce in an orderly fashion. The leukaemia cells do not mature, and therefore are not able to function as immune cells, but they keep on dividing in the bone marrow.

The two most common types of leukaemia found in children are Acute Lymphoblastic Leukaemia (ALL) and Acute Myeloid Leukaemia (AML). Leukaemia accounts for about 35% of all childhood cancers.

pathophysiologyofleukemiaLeukaemia is notoriously difficult to treat as it often relapses and becomes resistant to treatment. Although treatment and cure rates have improved over the past 50 years, it is still fatal to most patients.

Even with all the progress, treatment for leukaemia is still painful and unpleasant especially for children. Cancer patients need to undergo chemotherapy, steroid use, radiation therapy and more. If the leukaemia does not respond to treatment, the patient may have to have a bone-marrow transplant, which means that a perfect match needs to be found, and that is not always easy to do.

Acute Myeloid Leukaemia (AML) is caused by an overproduction of immature white blood cells that are unable to function properly or fight infection, and interfere with normal blood cell production. Current cancer treatments stop the growth of cancer cells, but virtually always damage or destroy other healthy cells at the same time.

A recent study, published in the Proceedings of the National Academy of Sciences, might just offer hope though, revealing that it’s possible to make leukemia cells kill each other.

According to the report, the researchers from The Scripps Research Institute (TSRI) found that applying certain antibodies to AML cells triggered them to mature into natural killer cells that support the immune system. These natural killer cells then destroy related AML cancer cells, but leave unrelated cancer cells alone, prompting researchers to call the technique fratricidin therapy, according to IFL Science.

mor010149fig1The key is an extremely rare human antibody. Antibodies are proteins produced naturally by the human body’s immune system. They act as the “handcuffs” to the white blood cells’ “police,” sticking to foreign invaders like microbes and either directly neutralizing them or tagging them for destruction.

The discovery was actually made accidentally, while studying the behaviour of leukaemia cells in a petri dish. The scientists were attempting to find antibody therapies to treat people with immune cell deficiencies in which the bone marrow doesn’t produce enough white blood cells. The last thing they actually expected to see, however, was that a handful of these growth-induced antibodies were turning the immature bone marrow cells into completely different types, such as cells normally found in the nervous system.

The researchers then flooded a human blood sample rich in dangerous AML cells with these growth-activating antibodies, and what they found was extraordinary: the antibodies transformed the AML cells into dendritic cells, key support cells within the immune system.

The longer the cells were exposed to the antibodies, the more they matured into cells that resemble, and behave similarly to, cells that hunt down and kill threats in the body, including Cell-differentiation-in-ALLviruses, bacteria and cancer cells.

These Natural Killer (NK) cells destroyed 15% of their cancerous kin in a single day in one sample , suggesting that a safer, more effective form of treatment could be well on its way. What is even better is that the NK cells were targeting only their former AML cell type, not other types of cancer cells because they already carry a genetic marker that identifies those particular cancer cells.

In their report published in the journal Proceedings of the National Academy of Sciences, the team said that, “We show here that cancerous cells from B-ALL patients can be reprogrammed, causing them to change into cells that resemble normal macrophages and can perform macrophage-associated functions such as the consumption of bacteria. Importantly, unlike typical B-ALL cells, these reprogrammed cells are no longer able to cause disease in immunodeficient mice. Finally, we show that this reprogramming process may occur to some degree in patients with B-ALL. This indicates that reprogramming B-ALL cells into macrophages might represent a previously unidentified therapeutic strategy.

The peculiar dynamics of fratricidin therapy, in which every cancerous cell is potentially convertible to a cancer-killing NK cell, suggests that – if the strategy works – it might not just reduce the targeted cancer-cell population in a patient, but eliminate it altogether.

According to senior investigator Richard A. Lerner, Institute Professor and the Lita Annenberg Hazen Professor of Immunochemistry at TSRI;

 “It’s a totally new approach to cancer, and we’re working to test it in human patients as soon as possible. We’re in discussions with pharmaceutical companies to take this straight into humans after the appropriate preclinical toxicity studies.”


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