Symptoms
The possible signs and symptoms of chronic myeloid leukemia include:
- Fatigue
- Feeling sick
- Bleeding tendency
- Susceptibility to infectious diseases
- Lack of appetite, digestive problems, weight loss.
- Fever
- Night sweats
- Enlargement of the spleen and liver, pain.
- Disorders of hematopoiesis, bone marrow changes
- Pale skin
In the bone marrow and blood, a strong proliferation and accumulation of immature precursors of hematopoiesis is observed. The disease, unlike other leukemias, occurs mainly in adults and rarely in children. It is usually discovered in the chronic phase, which often manifests itself in the symptoms described and responds to medication. It can progress to an accelerated phase and blast crisis after a few years if left untreated, with a fatal outcome.
Causes
CML is a cancer of the blood cells that leads, among other things, to the increased and uncontrolled formation of altered and diseased white blood cells and platelets or their precursors. The Philadelphia chromosome can be detected in the affected cells. It results from the reciprocal translocation between the long arms of chromosomes 9 and 22. The shortened chromosome 22 is called the Philadelphia chromosome. This brings together two genes, namely the BCR gene (from chromosome 22) and the ABL gene (from chromosome 9). The expressed BCR-ABL protein is a constantly active tyrosine kinase, which is the molecular cause of chronic myeloid leukemia. It can be detected in approximately 90% of patients.
Diagnosis
Diagnosis is made by medical treatment based on patient history, physical examination, blood count, bone marrow tests, and laboratory tests, among other factors. The Philadelphia chromosome can be detected with a polymerase chain reaction (PCR).
Drug treatment
Since the introduction of imatinib (Gleevec) in 2001, drugs have become available that allow targeted treatment of the disease. The kinase inhibitors (BCR-ABL inhibitors) inhibit the BCR-ABL tyrosine kinase, which is causally involved in disease progression, leading to destruction of cancer cells. In subsequent years, additional BCR-ABL inhibitors were introduced (see under BCR-ABL inhibitors). The new agents can also be used in cases of resistance or intolerance to imatinib. The figure shows the binding of imatinib (Gleevec) to BCR-ABL (click to enlarge). Another treatment option is stem cell transplantation, which can cure the disease but is associated with high risk. Furthermore, cytostatic drugs such as hydroxycarbamide (Litalir) and immunomodulators such as interferon alfa are used.
