Haematology 4 - Chronic myeloproliferative neoplasms Flashcards
What is the target of imatinib?
Mutated tyrosine kinase (by BCR-ABL gene)
What is the normal role of janus kinases?
GF binds to receptors - activate JAK- they activate the STAT pathway, which promotes cell growth and replication
Associated with haemopoietic cells
How does JAK2 mutation cause uncontrollable replication?
No longer need growth factor to activate
In polycythaemia vera, what else will be abnormal on the FBC other than red cell count?
Pronounced thrombocytophilia and slight granulocytophilia
Recall some symptoms of polycythaemia vera
Due to hyperviscosity: - Headaches - visual disturbances - dyspnoea, fatigue Due to increased histamine release: - peptic ulcer - aquagenic pruritis Other: - Plethora - Erythromelalgia (red, painful extremities) - Gout - Retinal vein engorgement
What is the expected level of erythropoietin in polycythaemia vera?
Low
What mutation is present in all patients with polycythaemia vera?
JAK2 V617F
What do you see in BM trephine biopsy in PV?
- increased cellularity
- megakaryocyte abnormality
- increase in reticulin fibres
How should pseudopolychthaemia and polycythaemia vera be differentiated?
Isotype dilution method
- Polycythemia will have increased plasma, pseudo will have decreased
Recall 3 causes of increased EPO
Hypoxia
Uterine myoma
Renal cancer
Recall 3 causes of pseudopolycythaemia
Alcohol
Obesity
Diuretics
Recall 3 ways in which polycythaemia vera can be treated
- Venesection (keep HCT <45%)
- Cytoreductive therapy
- Aspirin to reduce thrombosis risk (keep plts <400 x 10^9/l)
What is idiopathic erythrocytosis?
An isolated erythrocytosis with low EPO, where JAK2 V617 mutation is absent (although JAK mutation in exon 12 may be present)
How should idiopathic erythrocytosis be treated?
Venesection only
What is the diagnostic criteria for essential thrombocytothaemia?
- Chronic myeloproliferative neoplasm with a sustained thrombocytosis > 600 x 10^9/L
- megakaryocyte clustering and abnormality
- no evidence of reactive thrombocytosis
- no other myeloproliferative disorder
- JAK2 V617F mutation (60%)
Which age group is most at risk of essential thrombocytothaemia?
Bimodal:
Small peak at 30y (M=F)
Larger peak at 55y (F>M)
What are the presentations for patients with essential thrombocytothaemia?
Thrombosis or bleeding?? paradoxically
Minor : headache, dizziness, visual disturbance, small splenomegaly
Is there a JAK2 mutation in essential thrombocytothaemia?
Yes in 60%
What is the treatment for essential thrombocytothaemia?
1st line: Hydroxycarbamide (suppresses other cells too)
2nd line: anagreline (specific inhibition of plt formation - but SE = palpitation, flushing, increased risk of myelofibrosis)
Aspirin
Which condition is “tear drop poikilocytosis” pathognemonic of?
Myelofibrosis
What is seen in BM trephine biopsy in myelofibrosis?
- dry tap
- increased reticulin and collagen fibres
- prominent megakaryocyte hyperplasia and clustering
- new bone formation
Which cells are hyperproliferating in myelofibrosis?
Mostly megakaryocytes and granulocytes
Recall signs and symptoms of myelofibrosis
Massive spleen
Anaemia, thrombocytopenia/thrombocytosis
Hepatomegaly
Hypermetabolic state - wt loss, fatigue, dyspnoea, night sweats, hyperuricaemia
What is the treatment for myelofibrosis?
Supportive: RBC and plt transfusion
Hydroxycarbamide for thrombocytosis (may worsen anaemia)
Ruxolotinib - a JAK2 inhibitor
Allogenic stem cell transplant
Splenectomy (symptomatic relief but will worsen condition)
What are the bad prognosis signs in myelofibrosis?
- severe anaemia (<10g/dl)
- thrombocytopenia ( <100 x 10^9/l)
- massive splenomegaly
Recall 3 bad prognostic indicators in CLL
LDH raised
CD38+
11q23 deletion
Recall 3 good prognostic indicators in CLL
Hypermutated Ig gene
Low ZAP-70 expression
13q14 deletion
What is the 1st line treatment for CLL with a p53 deletion?
Ibrutinib
