Haematology 4 - Chronic myeloproliferative neoplasms

Question 1

What is the target of imatinib?

Answer 1

Mutated tyrosine kinase (by BCR-ABL gene - t(9;22) Philadelphia chromosome)

Used as a treatment for CML

Question 2

What is the normal role of janus kinases?

Answer 2

They activate the STAT pathway, which promotes cell growth and replication

Question 3

How does JAK2 mutation cause uncontrollable replication?

Answer 3

No longer need growth factor to activate

Question 4

In polycythaemia vera, what else will be abnormal on the FBC other than red cell count?

Answer 4

Pronounced thrombocytophilia and slight granulocytophilia

Question 5

Recall some symptoms of polycythaemia vera

Answer 5

Due to hyperviscosity: 
- Headaches
- visual disturbances
- dyspnoea
Due to increased histamine release: 
- peptic ulcer
- aquagenic pruritis

Question 6

Recall four clinical findings in polycythaemia vera

Answer 6

Plethora
Erythromelalgia (red, painful extremities)
Gout
Retinal vein engorgement

Question 7

What is the expected level of erythropoietin in polycythaemia vera?

Answer 7

Low

In secondary polycythaemia, erythropoietin will be raised (due to some physiological stimulus)

Question 8

What mutation is present in all patients with polycythaemia vera?

Answer 8

JAK2

Question 9

How should pseudopolycythaemia and polycythaemia vera be differentiated?

Answer 9

Isotype dilution method

Red cell mass is increased in true polycythaemia

Question 10

Recall 3 causes of increased EPO

Answer 10

Hypoxia
Uterine myoma
Renal cancer

Question 11

Recall 3 causes of pseudopolycythaemia (reduced plasma volume)

Answer 11

Alcohol
Obesity
Diuretics

Question 12

Recall 3 ways in which polycythaemia vera can be treated

Answer 12

1. Venesection
2. Cytoreductive therapy (hydroxycarbamide)
3. Aspirin to reduce thrombosis risk

Question 13

What is idiopathic erythrocytosis?

Answer 13

An isolated erythrocytosis with low EPO, where JAK2 V617 mutation is absent (although JAK mutation in exon 12 may be present)

Question 14

How should idiopathic erythrocytosis be treated?

Answer 14

Venesection only

Question 15

How is essential thrombocytothaemia defined?

Answer 15

Chronic myeloproliferative neoplasm with a sustained thrombocytosis > 600 x 10^9/L

Question 16

Which age group is most at risk of essential thrombocytothaemia?

Answer 16

Bimodal:
Small peak at 30y (M=F)
Larger peak at 55y (F>M)

Question 17

What are the 2 most likely presentations for patients with essential thrombocytothaemia?

Answer 17

Thrombosis

or bleeding?? paradoxically

Question 18

Is there a JAK2 mutation in essential thrombocytothaemia?

Answer 18

Yes in 50%

Question 19

What is the best treatment for essential thrombocytothaemia?

Answer 19

Hydroxycarbamide

Question 20

Which condition is “tear drop poikilocytosis” pathognemonic of?

Answer 20

Myelofibrosis

Question 21

Which cells are hyperproliferating in myelofibrosis?

Answer 21

Mostly megakaryocytes and granulocytes

Question 22

Recall 2 signs of myelofibrosis

Answer 22

Extramedullary haematopoiesis leads to a massive spleen and hepatomegaly

Anaemia and thrombocytopenia

Question 23

What is the best treatment for myelofibrosis?

Answer 23

Ruxolotinib - a JAK2 inhibitor

Question 24

Recall 3 bad prognostic indicators in CLL

Answer 24

LDH raised
CD38+
11q23 deletion

Question 25

Recall 3 good prognostic indicators in CLL

Answer 25

Hypermutated Ig gene
Low ZAP-70 expression
13q14 deletion

Question 26

What is the 1st line treatment for CLL with a p53 deletion?

Answer 26

Ibrutinib