9 out of 10 leukemias are treatable, but the remainder pose a huge challenge. A rare type of leukemia can evade current treatments and remain harmful while others can benefit from therapies, and scientists now believe they know why. Dubbed “chameleon cancer”, the cancerous cells are thought to be able to change their appearance to evade immune responses, lying low in the body and becoming a different type of blood cancer than is incredibly hard to treat. Researchers looked into why 9 out of 10 leukemia cases are treatable, but the remaining ones do not respond to treatment. These cancers can alter proteins on the surface of cells which signal the immune system that the cells are cancerous, or even entirely change to a different form of leukemia that is tough to treat. This is thought to involve the gene MLL/AF4, which is a fusion gene – a gene made by joining parts of two different genes together. Leukemia with MLL/AF4 originates in the womb and is incredibly aggressive, representing high risk to those with the disease. While it was known that cancers with this gene can make the switch to a more aggressive form, doctors are unsure why, and illuminating that mechanism could allow treatments to target and prevent it. “ALL cells carrying this chromosomal rearrangement have long been known to be able to relapse as a different type of blood cancer, acute myeloid leukaemia (AML). When this switch occurs, the leukaemia becomes extremely difficult to treat,” said co-author Simon Bomken, in a statement. “By studying MLL/AF4 leukemias we showed that the switch can happen in blood cells throughout different stages of development in the bone marrow. Importantly, the switch can be a result of additional genetic changes that can be caused by chemotherapy itself. As a consequence, some leukemias completely ‘re-programme’ themselves and switch identity from one cell type to another.” Diving into the mechanisms behind why this switch might occur, the researchers discovered that another gene could be controlling the switch: CHD4, which is already implicated in the development of AML. The implications of such a discovery could enable identification of cases that are at risk of jumping to AML, as well as potentially suppressing the genes responsible to keep the leukemia treatable. “In time specific therapies may become available to help prevent or overcome leukaemic switching and prevent the chameleon from changing its colours,” Dr Bomken continued. Source
