It’s terrifying when you first hear that you have a form of leukemia called CML (for chronic myelogenous leukemia). But there have been remarkable advances in treatment over the past two decades and now the prospects are very good for people living with the disease.
Leukemia means an excess (an “emia”) of white blood cells (or leukocytes; “leukos”=white). “Myelogenous” means the problem originates in the bone marrow. When people think of leukemia it is typically the acute form that often affects children and adolescents. The chronic form – CML – is a very different disease that is usually caused by a specific mutation.
The cells in our body are constantly growing and dividing to form new cells. As part of this process, the twin strands of DNA (the master blueprint containing our genetic code) separate into single strands. Each strand is then copied so that when the cell divides, each new cell will have its own double-stranded DNA. Unzipping DNA and forming new versions can lead to errors. In facts, with the billions of cell divisions that occur in our lifetime, countless mistakes are made. The body is able to correct these errors or destroy defective cells before they cause any problems. But in CML the mistake isn’t caught.
During cell division, two of the chromosomes (a DNA strand containing genes) exchange pieces of each other. Chromosome 22 snaps off at a place called the breakpoint cluster region (or BCR), and is replaced by a piece of chromosome 9 (a gene called ABL). This fusing of BCR with ABL creates a cancer gene called BCR-ABL, which is found in most people with CML. Meanwhile, chromosome 22 gets cheated in the exchange and ends up as a shortened version of itself. This short chromosome is called the Philadelphia chromosome, so-named because it was first identified at the University of Pennsylvania.
Genes are tiny manufacturing plants that mass produce proteins that serve a variety of functions in the body. What BCR-ABL produces are signalling molecules (called BCR-ABL transcripts). The signals tell white blood cells (WBCs) in the bone marrow to grow and divide. In a sense, the switch gets stuck in the On position and the result is a massive overproduction of WBCs.
In normal circumstances, the body has about 4.5 to 7 billion WBCs in a litre of blood. With the BCR-ABL stimulus, this number can become 10-fold higher or more. These WBCs spill out into the blood and can clog the spleen – which you feel as pain in the upper left part of your abdomen. Overproduction of WBCs in the tight confines of the bone marrow can also crowd out the production of other blood cells, such as red blood cells and platelets. This can cause anemia and clotting problems, which you experience as fatigue and bruising.
If CML is allowed to proceed unchecked, an increasing number of WBCs leave the production line before they have fully matured. They aren’t up to the many tasks that WBCs perform (such as fighting infection). Initially, this is called the accelerated phase. Once 30% of WBCs in your blood are immature, this is called the blast phase of CML. This blast phase (or “blast crisis”) must be avoided at all costs because the outlook is very poor once CML has progressed this far.