5. Myeloproliferative neoplasms

Question 1

What are myeloproliferative neoplasms? Name examples.

Answer 1

Group of BM diseases in which excess cells are produced - overproduction of one or several blood elements with dominance of a transformed clone.

• essential thrombocythaemia = overproduction of platelets by megakaryocytes
• polycythaemia vera = overproduction of RBCs
• myelofibrosis = replacement of haematopoietic tissue by CT leading to pancytopenia

Question 2

What causes myeloproliferative neoplasms?

Answer 2

• Mutations in myeloid lineage precursors - multipotent haematopoietic stem cells.
• Point mutation in gene coding for JAK2 (janus kinase 2) on chromo. 9 = cytoplasmic tyrosine kinase which causes increased proliferation and survival of haematopoietic precursors.

Question 3

What are the clinical features of myeloproliferative neoplasms?

Answer 3

Overlapping clinical features:

1. overproduction of one or several blood elements with dominance of a transformed clone
2. hypercellular marrow/marrow fibrosis
3. cytogenic abnormalities
4. thrombotic and/or haemorrhagic diatheses
5. extramedullary haematopoiesis (liver/spleen)

Question 4

What disease can myeloproliferative neoplasms develop into?

Answer 4

acute leukaemia

Question 5

What is polycythaemia (or erythrocytosis)?

Answer 5

• haematocrit (volume % of RBCs in blood) exceeds 55%
• can arise from:
  1) increased no of RBCs (absolute polycythaemia)
  2) decreased plasma volume (relative polycythaemia)

Question 6

What are the different types of absolute erythrocytosis?

Answer 6

1. Primary - polycythaemia vera
2. Secondary - driven by EPO production. Can be:
   - physiologically appropriate (in response to tissue hypoxia eg. at high altitude)
   - physiologically innapropriate
3. or due to an abnormal high affinity Hb

Question 7

Why might there be high levels of EPO in the blood?

Answer 7

1. central hypoxia
   - chronic lung disease (smoking)
   - R to L shunts
   - training at altitude
   - CO poisoning
2. renal hypoxia
   - renal artery stenosis
   - polycystic disease
3. tumours producing too much EPO, e.g. hepatocellular carcinoma
4. athlete EPO injection

Question 8

What are the clinical features associated with polycythaemia vera?

Answer 8

Essentially result from blood being thicker, e.g.

1. venous and arterial thrombosis
2. haemorrhage into skin or GI tract
3. splenic discomfort, splenomegaly
4. gout and arthritis
5. pruritus and burning pain in hands and feet

Question 9

Which conditions can polycythaemia vera develop into?

Answer 9

myelofibrosis or acute leukaemia

Question 10

What is the treatment for polycythaemia vera?

Answer 10

1. phlebotomy (venesection) to maintain haematocrit 45%
2. aspirin (anti-platelet effects)
3. cytoreduction using agents such as hydroxyurea (oral antimetabolite that inhibits DNA synthesis) should be considered if P has poor tolerance of venesection, shows symptomatic or progressive splenomegaly, other evidence of disease progression (e.g. weight loss, night sweats) or thrombocytosis.