Chronic myeloid leukaemia (CML) Flashcards
What is CML?
Proliferation of myeloid cells - granulocytes and their precursors, other lineages (platelets)
Aetiology of CML?
Cytogenic change that is characteristic of CML is the Philadelphia chromosome, a translocation of genes between chromosome 9 and 22: it is a t(9:22) translocation
- Results in a new gene – BCR-ABL1
What are the 3 typical phases of CML?
Chronic phase
Accelerated phase
Blast phase
What is the chronic phase of CML?
Can last around 5 years, often asymptomatic and patients are diagnosed incidentally with a raised WBC count.
What is the accelerated phase of CML?
Occurs where the abnormal blast cells take up a high proportion of the cells in the blood (10-20%) and bone marrow.
In the accelerated phase, patients become more symptomatic, develop anaemia and thrombocytopenia and become immunocompromised.
What is the blast phase of CML?
The blast phase follows the accelerated phase and involves an even higher proportion of blast cells (>30%)
This phase often has severe symptoms and pancytopenia.
Often fatal
Clinical features of CML?
Asymptomatic
Splenomegaly
Hypermetabolic symptoms i.e. weight loss, tachycardia, sweating, fatigue and reduced appetite.
Gout - caused by high cell turnover rate giving high urate
Others: problems with priapism, hyperleukocytosis (abnormally high blast cell count)
Blood tests for CML?
FBC: normal or decreased Hb, increased WBC, platelets can be low, normal or raised.
- Exclude other causes of raised granulocytes e.g. infection, post-surgery, steroids.
Blood film: neutrophilia i.e. abnormally high neutrophil count, with myeloid precursors including blasts.
Bone marrow biopsy details for CML?
Not generally required for diagnosis but would show increased cellularity with increased granulocytes etc.
FISH used to look for cytogenic abnormality. Cytogenics can show Philadelphia chromosome in 97% of cases (can be tested in blood or bone marrow).
Management of CML?
Fatal without stem cell/bone marrow transplant in chronic phase.
Durable treatment responses with tyrosine kinase inhibitors e.g. imatinib.
- Prevents action of BCR-ABL fusion protein i.e. this is the abnormal protein produced by the Ph mutation.
What are the key features of each of the leukaemia types?
ALL is the most common leukaemia in children and is associated with Down syndrome
CLL is associated with warm haemolytic anaemia, Richter’s transformation and smudge cells
CML has three phases, including a long chronic phase, and is associated with the Philadelphia chromosome
AML may result in a transformation from a myeloproliferative disorder and is associated with Auer rods
What is Ph mutation?
A mutation forming an abnormal chromosome known as the philadelphia chromosome.
This is when there is a translocation mutation.
Made when pieces of chromosomes 9 and 22 break off and trade places.
What is BCR-ABL1?
A fusion gene.
This fusion gene is made when part of the ABL gene on chromosome 9 breaks off and attaches to the BCR gene on chromosome 22.
Forming the BCR-ABL1 fusion gene on the abnormal philadelphia chromosome.
