CML and Myeloproliferative Disorders Flashcards
What is polycythaemia?
Raised Hb concentration and Haematocrit %
What are causes of polycythaemia?
Relative: Lack of plasma - Non-malignant
True: Excess erythrocytes
- Secondary: Non-malignant
- Primary: Myeloproliferative neoplasm
What are examples of myeloproliferative neoplasms?
Ph (Philadelphia Chromosome) negative:
- Polycythaemia vera (PV)
- Essential Thrombocythaemia (ET)
- Primary Myelofibrosis (PMF)
Ph positive:
- Chronic myeloid leukaemia (CML)
What are dilution studies?
To differentiate between true and relative polycythaemia
Red Cell Mass: 51Cr labelled RBC
Plasma Vol: 131I labelled albumin
What are causes of relative/pseudo-polycythaemia?
Alcohol
Obesity
Diuretics
What happens to EPO in primary and secondary true polycythaemia?
Primary: Reduced
Secondary: Elevated
What are appropriate causes of elevated EPO?
High altitude
Hypoxic lung disease
Cyanotic heart disease
High affinity haemoglobin
What are inappropriate causes of elevated EPO?
Renal disease (cysts, tumours inflammation)
Uterine myoma
Other tumours (liver, lung)
What are examples of myeloid haematological malignancies?
Acute myeloid leukaemia (blasts >20%)
Myelodysplasia (blasts 5-19%)
Myeloproliferative disorders:
- Essential thrombocythaemia (megakaryocyte)
- Polycythemia vera (erythroid)
- Primary myeofibrosis
Chronic myeloid leukaemia
What are examples of lymphoid haematological malignancies?
Precursor cell malignancy:
- Acute lymphoblastic leukaemia (B & T)
Mature cell malignancy:
- Chronic Lymphocytic leukaemia
- Multiple myeloma
- Lymphoma (Hodgkin & Non Hodgkin)
Which processes are disrupted by mutation?
Cellular proliferation (type 1)
Impair/block cellular differentiation (type 2)
Prolong cell survival (anti-apoptosis)
Mutation mechanisms:
- DNA point mutations
- Chromosomal translocations:
- Creation of novel fusion gene
- Disruption of proto-oncogene
What is the normal function of tyrosine kinases?
Transmit cell growth signals from surface receptors to nucleus.
Activated by transferring phosphate groups to self and downstream proteins.
Normally held tightly in inactive state.
Promote cell growth do not block maturation.
What happens when mutations cause activation of tyrosine kinase?
Expansion increase in mature/end cells
Red cells: Polycythaemia
Platelets: Essential thrombocythaemia
Granulocytes: Chronic myeloid leukaemia
Which genes are associated with myeloproliferative neoplasms?
JAK2
Calreticulin
MPL
How is the diagnosis of myeloproliferative disorder (Ph negative) made?
Based on combination of:
Clinical features:
- Symptoms
- Splenomegaly
FBC +/- Bone marrow biopsy
Erythropoietin level (EPO)
Mutation testing: Phenotype linked to acquired mutation
What is the epidemiology of polycythaemia vera?
Annual incidence 2-3/100000
Slightly more in males 1.2:1
Mean age at diagnosis 60 years
5% below age of 40 years