Chronic Myeloid Leukaemia (CML) Flashcards
what is chronic myeloid leukaemia (CML)?
- a cancer of white blood cells that is characterised by the uncontrolled growth of myeloid cells in the bone marrow
- this uncontrolled growth leads to myeloid cells crowding out the bone marrow and interfering with the production of normal blood cells (e.g. platelets, erythrocytes and neutrophils)
- the abnormal myeloid cells spill into the peripheral blood. this is reflected in the full blood count which demonstrates abnormally raised levels of mature granulocytes (e.g. neutrophils, basophils and eosinophils)
what is the aetiology of CML?
a translocation between parts of chromosome 9 and 22, which leads to the formation of the so-called philadelphia chromosome
what is the pathophysiology of CML?
- a gene contained on chromosome 22 called BCR fuses with a gene on chromosome 9 known as ABL
- this creates a hybrid gene known as BCR-ABL
- BCR-ABL can add phosphates to tyrosine residues (a tyrosine kinase) and this allows the gene to activate a cascade of proteins that control the cell cycle, speeding up cell division
- the BCR-ABL protein inhibits DNA repair, causing genomic instability and making the cell more susceptible to developing further genetic abnormalities
what are the symptoms of CML?
- often asymptomatic
- upper abdominal pain (e.g. hepatosplenomegaly)
- anorexia
- low-grade fever
- night sweats
- gout (e.g. uric acid)
- increased susceptibility to infections
- anaemia (e.g. SOB)
- petechiae (e.g. thrombocytopenia)
- neurological deficit (e.g. leucocytosis)
what are the findings on examination of CML?
- pallor
- hepatosplenomegaly
- bruising/petechiae
what are the laboratory investigations for CML?
- FBC (e.g. leucocytosis, ↑ eosinophils, ↑ basophils, ↑ granulocytes, anaemia)
- U&Es
- LDH
- urate
- blood film (e.g. all stages of granulocyte maturation noted)
why is bone marrow aspiration necessary in the diagnosis and staging of CML?
to stage disease (e.g. the percentage of blasts determines chronic, accelerated, or blast crisis) and enables cytogenetic sampling to confirm the diagnosis (e.g. presence of philadelphia chromosome)
what is the gold standard for diagnosing CML, and how is the philadelphia chromosome detected?
- detecting the philadelphia chromosome (e.g. present in 95% of CML)
- it is identified using FISH or PCR
what are the three stages of CML according to the WHO?
- chronic
- accelerated
- blast
what characterises the chronic phase of CML?
- approximately 85% of patients with CML are in the chronic phase at the time of diagnosis
- patients are usually asymptomatic or have only mild symptoms of fatigue or abdominal fullness
- duration of the chronic phase is variable and without treatment, the disease will usually progress to the accelerated phase due to the accumulation of genetic mutations in addition to the BCR-ABL gene
what characterises the accelerated phase of CML?
a patient is said to be in the accelerated phase when any of the following are present:
- 10 – 19% myeloblasts in the blood or bone marrow
- > 20% basophils in the blood or bone marrow
- platelet count <100,000, unrelated to therapy
- platelet count >1,000,000, unresponsive to therapy
- cytogenetic evolution with new abnormalities in addition to the philadelphia chromosome
- increasing splenomegaly or white blood cell count, unresponsive to therapy
what characterises the blast crisis of CML?
is diagnosed if any of the following are present in a patient with CML:
- > 20% myeloblasts or lymphoblasts in the blood or bone marrow
- large clusters of blasts in the bone marrow on biopsy
- development of a chloroma (e.g. a solid focus of leukaemia outside the bone marrow)
what is the management of CML?
- tyrosine kinase inhibitor (e.g. imatinib)
- bone marrow transplantation
what is the mechanism of action of tyrosine kinase inhibitors (e.g. imatinib)?
- target BCR-ABL, blocking the ability of the gene to phosphorylate a tyrosine
- this inhibits the proliferation of malignant cells
