Chronic Myeloid Leukaemia Flashcards
What cell types are involved in the proliferation of chronic myeloid leukaemia (CML)?
Granulocytes and their precursors, as well as other lineages like platelets
Define Chronic Myeloid Leukaemia
Proliferation of myeloid cells - granulocytes and their precursors, other lineages (platelets)
What is the cytogenetic change characteristic of CML?
The Philadelphia chromosome, resulting from a t(9:22) translocation
What is the product of the BCR-ABL1 gene, and what is its role?
A tyrosine kinase, which causes abnormal phosphorylation leading to haematological changes in CML
What are the three phases of CML?
Chronic phase
Accelerated phase
Blast phase
Describe the chronic phase of CML.
Often asymptomatic, lasting around 5 years, with diagnosis typically incidental due to a raised WBC count
What occurs in the accelerated phase of CML?
Increased blast cells (10–20%), anaemia, thrombocytopenia, and immunosuppression with symptomatic disease
What characterises the blast phase of CML?
A high proportion of blast cells (>30%), severe symptoms, pancytopenia, and often fatal progression
What are common clinical features of CML?
(1) Asymptomatic
(2) Splenomegaly (early satiation)
(3) hypermetabolic symptoms
(4) Gout (from high urate)
(5) hyperleukocytosis
(6) Priapism
What are typical findings on a full blood count (FBC) in CML?
- Normal or decreased Hb
- Raised WBC
- Platelets that may be low, normal, or raised
What is seen on a blood film in CML?
Neutrophilia with myeloid precursors, including blasts
What is the significance of leukocyte alkaline phosphatase (LAP) in CML?
LAP is usually reduced
How is the Philadelphia chromosome detected in CML?
Using FISH or cytogenetics
What is the first-line treatment for CML?
Tyrosine kinase inhibitors, such as imatinib
How do tyrosine kinase inhibitors work in CML?
They prevent the action of the BCR-ABL fusion protein
What is required in the chronic phase if tyrosine kinase inhibitors fail?
A stem cell/bone marrow transplant
What conditions are the t(9:22) translocation present in?
CML and ALL
A 52-year-old male patient presents to the general practitioner with a 4-week history of weight loss and malaise. He also reports discomfort in the left upper abdomen and abdominal fullness. There is no past medical history noted. He denies any recent travel.
On physical examination, a mass is arising from the left upper quadrant, extending to the right iliac fossa. The mass has a palpable notch and a dull percussion note.
What blood film findings are consistent with the most likely diagnosis?
Mature myeloid cells
= CML typically presents in middle-aged patients with massive splenomegaly
A 53-year-old female presents to the general practitioner with a 6-week history of malaise and a 3kg weight loss. She also reports early satiety and abdominal discomfort. There is no past medical history of note and no recent travel history.
On physical examination, there is a palpable mass arising from the left upper quadrant and extending to the right iliac fossa. The mass moves with respiration and has a dull percussion note.
Where in the above text is splenomegaly mentioned/ described?
(1) Early satiety and abdominal discomfort, which are symptoms often associated with splenomegaly
(2) A palpable mass arising from the left upper quadrant and extending to the right iliac fossa, which is consistent with an enlarged spleen
(3) The mass moves with respiration and has a dull percussion note, both characteristic of splenomegaly
A 58-year-old woman presents to her GP with generalised fatigue and night sweats which is investigated. She is diagnosed with chronic myeloid leukaemia (CML).
What is the mainstay of pharmacotherapy for Philadelphia chromosome-positive CML?
Imatinib
A 55-year-old woman presents with fatigue, night sweats, and unintentional weight loss. Blood tests reveal an elevated white blood cell count and decreased platelets. A bone marrow biopsy confirms the diagnosis of a blood cancer characterised by abnormal white blood cells in the bone marrow and blood.
What is the most likely diagnosis? and why is that your answer?
Leukaemia
= Leukaemia is a group of blood cancers characterised by abnormal white blood cells in the bone marrow and blood. Symptoms include fatigue, fever, night sweats, and weight loss. Blood tests reveal an elevated white blood cell count and decreased platelets. A bone marrow biopsy confirms the diagnosis
If the question mentions basophilia or t(9;22)
CML
If it mentions smudge cells or lymphadenopathy
CLL
Main characteristic difference between CML and CLL
CML - involves BCR-ABL fusion protein
CLL- Deletion of the long arm of chromosome 13q
What is the treatment of choice for chronic myeloid leukaemia?
Imatinib
Cytogenetic testing confirms the presence of the BCR-ABL1 fusion gene.
What finding is expected to be observed in further investigation?
Myelocytosis
