Understanding CML

What is chronic myeloid leukaemia?

Chronic myeloid leukaemia (CML) is a condition where cells in the bone marrow that normally develop into white bloods cells such as neutrophils, basophils, eosinophils, and monocytes don’t develop properly and become abnormal. These abnormal cells grow and divide at a higher rate than normal cells. They also do not die when they become old or damaged like normal cells do. This is why CML is sometimes referred to as a blood cancer. CML is also called chronic myelogenous, chronic granulocytic or chronic myelocytic leukaemia.1

What are the symptoms of CML?2

CML usually progresses slowly, so symptoms may not appear for a long time. In Europe about half of people are diagnosed without any symptoms through routine blood tests. CML can have the following signs and symptoms:2

  • Tiredness (fatigue)
  • Feelings of discomfort, illness or unease without an obvious cause (malaise)
  • Weight loss
  • Fever
  • Abdominal swelling, discomfort or feeling of fullness in the upper left part of the abdomen. This is caused by an enlarged spleen
  • Bone pain
  • Bleeding

What causes CML?1

Nearly all the cells in the body contain chromosomes, made up of genes. Genes are the coded instructions in cells for making new cells and controlling how cells behave. Sometimes a part of one chromosome breaks off and switches places with a piece from another chromosome (called a “translocation”). In CML, parts of the BCR gene on chromosome 22 swaps parts with the ABL1 gene on chromosome 9. A new fusion gene called BCR-ABL1 is formed. This gene is located on a new shortened chromosome 22, which is called the Philadelphia (Ph) chromosome.

This Ph chromosome triggers the cell to make a protein (called a ‘BCR-ABL transcript’ or a ‘tyrosine kinase’) that encourages abnormal white blood cells to grow. The Ph chromosome is detectible in 95 out of 100 people with CML and all people diagnosed with CML will have the BCR-ABL1 fusion gene. However, we currently don’t know why this translocation happens.

How is CML diagnosed?2

Diagnosis of CML is generally straightforward and can be done with a blood test. Confirmation of diagnosis is then done by identifying the Philadelphia chromosome or the BCR-ABL1 transcript, or both, in the blood or bone marrow cells.

Who gets CML?2

The average age at diagnosis in Europe is between 60 and 65 years. Many people are diagnosed at a younger age, but it is rare in children. The reason that some people develop CML is not known.

What are the different phases of CML?

  • CML cells are unstable and without effective treatment they easily develop further abnormalities.2 This is what causes the disease to progress.
  • Chronic phase: this phase is characterised by slow disease progression that can last several years.1 During this phase only a small number of white cells in the blood and bone marrow are immature (blast cells)3
  • Accelerated phase: during this phase, the disease progresses more quickly, treatments become less effective and CML symptoms worsen.1 In this phase there are an increased number of immature blast cells. These cells sometimes have additional damage and mutations in addition to the Ph chromosome3
  • Blast phase (also called blast crisis): a high number of immature CML cells (blasts) build-up in the bone marrow and blood. The disease becomes much worse. Symptoms include massive enlargement of the spleen, fever, weight loss, serious infections and excessive bleeding1
  • Resistant CML: Resistant CML is CML that returns after treatment or that doesn’t respond to treatment. This is different from CML that has developed resistance to a specific treatment only.3 It is important to remember that treatments for CML are often very effective. Nine out of 10 people diagnosed with CML are diagnosed during the chronic phase2 and most will never progress beyond chronic phase and will live long and healthy lives.
  1. References
    1. CML Support. What is CML? Available at: https://cmlsupport.org.uk/section/what-cml.
    Accessed August 2020.
    2. Hochhaus et al. 2017. Annals of Oncology. 28 (Supplement 4): iv41–iv51.
    3. Cancer.net. Leukemia - Chronic Myeloid - CML: Phases. Available at:
    https://www.cancer.net/cancer-types/leukemia-chronic-myeloid-cml/phases. Accessed August 2020.