Myeloproliferative Disorders

Question 1

What are myeloproliferative disorders?

Answer 1

Clonal haemopoietic stem cell disorders with increased production of one or more types of haemopoietic cells

Question 2

What are blood count signs suggesting myeloproliferative disorders?

Answer 2

High granulocyte/Hb/platelet count
Eosinophilia/basophilia
Splenomegaly

Question 3

In chronic myeloid leukaemia there is proliferation of which cells?

Answer 3

Myeloid cells

Question 4

Proliferation of myeloid cells leads to increased what?

Answer 4

Granulocytes

Question 5

What is the course of CML?

Answer 5

Chronic phase with intact maturation lasting 3-5 years then a blast crisis with maturation defect

Question 6

Give some clinical features of CML

Answer 6

Splenomegaly
Hypermetabolic symptoms (weight loss, fatigue etc.)
Gout

Question 7

What blood count changes are seen in CML?

Answer 7

Leucocytosis (neutrophilia/eosinophilia/basophilia)

Thrombocytosis

Question 8

What is the hallmark feature of CML?

Answer 8

Philadelphia chromosome

Question 9

Philadelphia chromosome occurs when?

Answer 9

There is a reciprocal translocation between chromsomes 9 and 22 causing a short chromosome 22

Question 10

What gene is caused by a Philadelphia chromosome?

Answer 10

BCR-ABL1

Question 11

What effect does BCR-ABL1 have?

Answer 11

Produces tyrosine kinase causing abnormal phosphorylation and haematological changes

Question 12

Give examples of BCR-ABL1 negative myeloproliferative disorders

Answer 12

Essential thrombocythaemia
Polycythaemia rubra vera
Idiopathic myelofibrosis

Question 13

Give some common features of myeloproliferative disorders

Answer 13

Increased cell turnover - causes gout/fatigue/weight loss
Splenomegaly
Marrow failure
Thrombosis

Question 14

What are the diagnostic features of polycythaemia rubra vera?

Answer 14

High Hb/haematocrit accompanied by erythrocytosis

Question 15

In PRV there is a mutation in which gene?

Answer 15

JAK2

Question 16

Mutational analysis is now part of initial screening for PRV. True/false?

Answer 16

True

Question 17

Give some clinical features of PRV

Answer 17

MPD features
Headache/fatigue
Itch

Question 18

What is used to treat PRV?

Answer 18

Venesection (HCT <0.45)
Aspirin
Cytotoxic oral chemotherapy

Question 19

What occurs in essential thrombocythaemia?

Answer 19

There is uncontrolled production of abnormal platelets

Question 20

What are the main clinical features of essential thrombocythaemia?

Answer 20

Increased cell turnover
Thrombosis
Bleeding (surgery)

Question 21

Essential thrombocythaemia has mutations in which genes?

Answer 21

JAK2 (in 50%)

CALR (in those without mutant JAK2)

Question 22

What is the treatment for essential thrombocythaemia?

Answer 22

Anti-platelet (aspirin)
Cytoreductive therapy (hydroxycarbamide)

Question 23

Give some features of idiopathic myelofibrosis

Answer 23

Marrow failure (anaemia/bleeding)
Splenomegaly (LUQ pain etc.)
Hypercatabolism

Question 24

How does myelofibrosis appear on blood film?

Answer 24

Tear-drop shaped RBC

Question 25

What is the treatment for myelofibrosis?

Answer 25

Supportive care
Allogenic stem cell transplantation
JAK2 inhibitors