Myeloproliferative disorders

Question 1

What occurs to make the BCR-ABL1 gene positive?

Answer 1

There is a chromosome translocation between 9 and 22 that means that BCR is sitting right next to ABL, predisposing to CML

Question 2

In which myeloproliferative disorder is the BCR-ABL1 gene positive?

Answer 2

Chronic myeloid leukaemia

Question 3

What is another name for the BCR-ABL1 gene?

Answer 3

The Philadelphia chromosome

Question 4

What three disorders are BCR-ABL1 negative?

Answer 4

Idiopathic myelofibrosis
Essential thrombocythaemia
Polycythaemia rubra vera

Question 5

What is chronic myeloid leukaemia?

Answer 5

A disease in which there is increased proliferation of myeloid cells - mainly granulocytes, but platelets can also be raised

Question 6

What was previously the clinical course of CML?

Answer 6

Chronic phase: high numbers of mature cells continued to proliferate for 3-5 years

Acute phase: maturation of cells began to be affected, so a phase was entered resembling acute leukaemia - ‘blast crisis’

Question 7

How might CML present?

Answer 7

Asymptomatic
Splenomegaly, can cause early satiety
Weight loss
Fever
Gout
Night sweats
Priapism, retinal bleeds, sluggish circulation in CNS can be caused by very high white cell count

Question 8

What changes might appear on blood count in CML?

Answer 8

Normal or low Hb
Leucocytosis with neutrophilia and myeloid precursors, basophilia, eosinophilia
Thrombocytosis

Question 9

What is the problem in the Philadelphia chromosome that causes CML?

Answer 9

The gene product is tyrosine kinase which causes abnormal signalling pathways that result in proliferation due to increased gene activity

Question 10

How can CML due to the BCR-ABL1 gene be treated with target therapy?

Answer 10

Tyrosine kinase inhibitors - e.g imatinib

Question 11

What symptoms are associated with myeloproliferative disorders?

Answer 11

Asymptomatic
Bone pain
Gout 
Night sweats
Weight loss
Fatigue 
Splenomegaly (splenic infarction - abd pain)
Marrow failure (myelofibrosis)
Thrombosis (MI, TIA, stroke)

Question 12

What is polycythaemia rubra vera?

Answer 12

A disorder in which there is over production of red cells

Question 13

What would blood count show in polycythaemia rubra vera?

Answer 13

High haemoglobin
High haematocrit
Erythrocytosis
May also have high white cell count and high platelet count

Question 14

What is it important to distinguish polycythaemia rubra vera from?

Answer 14

Pseudopolycythaemia (dehydration, diuretic treatment)
Secondary polycythaemia (smoking, chronic hypoxia, Epo-secreting tumour)

Question 15

Why does dehydration and diuretic treatment cause pseudopolycythaemia?

Answer 15

Reduced plasma volume makes Hb and haematocrit seem higher than they are - concentrating effect

Question 16

What symptoms are associated with polycythaemia rubra vera?

Answer 16

Other MPD symptoms
Headache
Fatigue
Itch/aquagenic pruritis

Question 17

What gene mutation is associated with polycythaemia?

Answer 17

JAK2

Question 18

What is JAK2?

Answer 18

JAK2 is a kinase present in 95% of patients with polycythaemia

Question 19

What happens to erythropoetin level in polycythaemia?

Answer 19

Reduced

Question 20

How is polycythaemia treated?

Answer 20

Venesect until haemocrit

Question 21

What is essential thrombocythaemia?

Answer 21

Uncontrolled production of abnormal platelets

Question 22

What is the clinical significance in the platelets being abnormal in essential thrombocythaemia?

Answer 22

Patients can present with thrombosis

But can also present with bleeding due to acquired Von Willebrand disease

Question 23

How is essential thrombocythaemia diagnosed?

Answer 23

Exclude reactive thrombosis
Genetic testing
Characteristic bone marrow appearance

Question 24

What might cause reactive thrombocythaemia?

Answer 24

Blood loss
Inflammation
Malignancy (particularly ovarian, GI)
Iron deficiency

Question 25

What genes are associated with essential thrombocythaemia?

Answer 25

JAK2 (positive in about 50%)
CALR (often positive if JAK2 negative)
MPL mutation

Question 26

How is polycythaemia treated?

Answer 26

None (if low risk)
Aspirin
Cytoreductive therapy (hydroxycarbamide, anagralide, interferon alpha)

Question 27

What is secondary myelofibrosis?

Answer 27

Myelofibrosis that is preceded by polycythaemia or thrombocytothaemia

Question 28

What are the pathological features of idiopathic myelofibrosis?

Answer 28

Marrow failure (variable degrees)
Bone marrow fibrosis in the absence of a secondary cause
Extramedullary haematopoiesis (liver or spleen)
Leukoerythroblastic blood
Tear drop shaped red blood cells

Question 29

What are the causes of secondary bone marrow fibrosis?

Answer 29

Lead
Arsenic
Infections e.g. TB

Question 30

What is leukoerythroblastic blood?

Answer 30

There are both erythroblasts and myeloid precursors/myelocytes in the blood at the same time

Question 31

What are the causes of leukoerythroblastic blood?

Answer 31

Reactive (sepsis)
Marrow infiltration
Myelofibrosis

Question 32

What are the clinical features of myelofibrosis?

Answer 32

Marrow failure - anaemia, bleeding, infection
Splenomegaly - LUQ pain, portal hypertension
Hypercatabolism - weight loss, bone pain

Question 33

What condition is tear drop polikocytes seen in?

Answer 33

Myelofibrosis

Question 34

What condition can be diagnosed with biopsy and congo red stain?

Answer 34

Amyloidosis

Question 35

What scan is used for amyloidosis?

Answer 35

SAP scan

Question 36

What is Waldenstrom’s macroglobulinaemia?

Answer 36

A myelodysplastic disorder producing IgM - more immature than lymphoma