What is chronic myeloid leukaemia (CML)?
Leukaemia is a haematological malignancy (blood cancer) that develops in the bone marrow, blood, the lymphatic system and other tissues. The types of leukaemia are commonly divided into acute and chronic, depending on the speed of progression of the disease.
In general, we speak of leukaemia in the presence of biological alterations in blood cells (red cells, white cells and platelets) that cause growth and uncontrolled proliferation of the cells themselves. The name derives from the Greek word leukemia leucos = white, because the disease begins in the white blood cells responsible for fighting infections, which normally reproduce according to the needs of the body.
In patients with leukaemia, the bone marrow produces large numbers of abnormal white blood cells, which have genetic mutations in the DNA and therefore they are not working properly. The causes of this disease are not yet fully understood, but both genetic and environmental factors appear to be involved.
Chronic types of leukaemia are more common in adults. The most common forms are chronic lymphocytic leukaemia (CLL) and chronic myeloid leukaemia (CML): it might be more appropriate to use the word "enzootic" in place of "leukaemia" given the clear differences in behaviour, response to therapy and prognosis from acute forms of leukaemia.
CML is very common in adults and very rare in infants with a median age of onset of around 60 years and an incidence in the population of about 2.3 new cases per year per 100,000 inhabitants, in apparent growth given the average increase in life expectancy.
The main characteristic of this disease is an abnormal proliferation of mature white blood cells, and more rarely platelets, which most often is found randomly on the occasion of periodic control examinations. In the past, when it was less common to undergo examinations, the diagnosis of CML arised from the feedback of feeling of weight to the left side due to the growth in the size of the spleen (splenomegaly) that still is associated with more advanced stages of CML.
What are the origins of this disease?
In 1960 there was a study of chromosomes (karyotyping) that brought two doctors of Philadelphia to find that patients with CML had chromosome 22 shorter than normal. This form of "short" chromosome 22 was called Philadelphia chromosome (Ph chromosome). Subsequent studies showed that, in patients with CML the chromosome 9 also proved different. It was found that between chromosome 9 and chromosome 22 was a mutual exchange of chromosomal material: namely, that a portion of chromosome 9 is linked to chromosome 22 and vice versa (translocation). The results were that all leukemic cells were positive for the translocation 9 and 22, while the other cells of the bone and tissue were those with normal karyotype.
In the 80s it was known that the translocation 9; 22 involved mainly two genes – the BCR gene (chromosome 22) and the ABL gene (chromosome 9) – which gave rise to the so-called fusion gene BCR-ABL. The latter gives rise to an abnormal protein (not present in healthy people), which significantly affects the cell cycle bringing the leukemic cells to a poorly controlled proliferation. The abnormal protein pursuing a "tyrosine kinase" continues to other proteins in the cell: the knowledge of this mechanism has led researchers to the discovery of specific drugs for the selective inhibition of its function (tyrosine kinase inhibitors) that have revolutionized care of CML with extraordinary success.
What are the risk factors for CML?
Some factors may increase the risk of developing certain types of leukaemia:
- Cancer therapies, such as certain types of chemotherapy or radiation therapy.
- Exposure to high levels of radiation
Prevention
Beyond avoiding exposure to radiation or cancer-causing chemicals, there is no specific way (lifestyle, eating habits or exposure to chemical agents) to prevent CML, since the exact causes are unknown.
