What if a minor DNA error made your body a constantly working cellular factory? This is, in effect, the case with Chronic Myeloid Leukemia (CML) where a minor mistake in your DNA has devastating consequences on your body's biology. At the center of CML is our bone marrow-the spongy tissue found inside bones where our blood cells are manufactured. Normally our cells undergo a precise and well-controlled life cycle of growth and division before death. In CML this finely tuned system is knocked off course by a genetic mistake. CML cannot be transmitted between individuals; there is not a viral or infectious agent to blame. At the root of CML lies a particular genetic mutation which occurs as a result of an abnormal chromosome configuration; called the Philadelphia chromosome. This is a chromosomal abnormality in which part of one chromosome is accidentally swapped for part of another (most commonly chromosomes 9 and 22).Although this seems a relatively small change, it profoundly alters our cells.


    A swap results in the fusion of genes BCR and ABL (hence the hybrid gene BCR-ABL) which codes for a protein that functions like an ‘on' switch which cannot be turned 'off'. In other words, your cells don't respond to the body's signal to stop growing and this leads to a vast increase in your number of white blood cells. Not only are there far too many white blood cells, but these white blood cells are immature and are thus incapable of doing their jobs. This increases your risk of infection, means you are not getting enough oxygen around your body and you cannot stop bleeding properly, potentially making it a very serious disease to have to battle. Your spleen is also likely to become very large, contributing to the symptoms. 






CML typically progresses slowly. 

    Over time the cells grow more uncontrollably and the disease can pass through distinct phases. When it's not progressing very fast, we call it chronic phase when there may be minimal or no signs and symptoms of illness. It can eventually lead to accelerated phase where symptoms progress faster, and finally to blast crisis which is an equivalent of an extremely advanced leukemia.

    Thankfully, modern medicine has seen the most amazing advances with regards to CML therapy. This is all thanks to the development of drugs known as tyrosine kinase inhibitors (TKIs) which are able to switch off the harmful BCR-ABL protein by blocking the 'on' switch and enabling those suffering with CML to live a full and rewarding life.

To put it in simple terms, CML highlights how a relatively minor genetic defect can lead to an uncontrolled cellular malfunction, but also proves how our understanding of disease at a molecular level has allowed for the development of powerful therapies that make an enormous difference to the lives of those who have the condition.