Myeloproliferative disorders Flashcards
(36 cards)
What occurs to make the BCR-ABL1 gene positive?
There is a chromosome translocation between 9 and 22 that means that BCR is sitting right next to ABL, predisposing to CML
In which myeloproliferative disorder is the BCR-ABL1 gene positive?
Chronic myeloid leukaemia
What is another name for the BCR-ABL1 gene?
The Philadelphia chromosome
What three disorders are BCR-ABL1 negative?
Idiopathic myelofibrosis
Essential thrombocythaemia
Polycythaemia rubra vera
What is chronic myeloid leukaemia?
A disease in which there is increased proliferation of myeloid cells - mainly granulocytes, but platelets can also be raised
What was previously the clinical course of CML?
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’
How might CML present?
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
What changes might appear on blood count in CML?
Normal or low Hb
Leucocytosis with neutrophilia and myeloid precursors, basophilia, eosinophilia
Thrombocytosis
What is the problem in the Philadelphia chromosome that causes CML?
The gene product is tyrosine kinase which causes abnormal signalling pathways that result in proliferation due to increased gene activity
How can CML due to the BCR-ABL1 gene be treated with target therapy?
Tyrosine kinase inhibitors - e.g imatinib
What symptoms are associated with myeloproliferative disorders?
Asymptomatic Bone pain Gout Night sweats Weight loss Fatigue Splenomegaly (splenic infarction - abd pain) Marrow failure (myelofibrosis) Thrombosis (MI, TIA, stroke)
What is polycythaemia rubra vera?
A disorder in which there is over production of red cells
What would blood count show in polycythaemia rubra vera?
High haemoglobin
High haematocrit
Erythrocytosis
May also have high white cell count and high platelet count
What is it important to distinguish polycythaemia rubra vera from?
Pseudopolycythaemia (dehydration, diuretic treatment) Secondary polycythaemia (smoking, chronic hypoxia, Epo-secreting tumour)
Why does dehydration and diuretic treatment cause pseudopolycythaemia?
Reduced plasma volume makes Hb and haematocrit seem higher than they are - concentrating effect
What symptoms are associated with polycythaemia rubra vera?
Other MPD symptoms
Headache
Fatigue
Itch/aquagenic pruritis
What gene mutation is associated with polycythaemia?
JAK2
What is JAK2?
JAK2 is a kinase present in 95% of patients with polycythaemia
What happens to erythropoetin level in polycythaemia?
Reduced
How is polycythaemia treated?
Venesect until haemocrit
What is essential thrombocythaemia?
Uncontrolled production of abnormal platelets
What is the clinical significance in the platelets being abnormal in essential thrombocythaemia?
Patients can present with thrombosis
But can also present with bleeding due to acquired Von Willebrand disease
How is essential thrombocythaemia diagnosed?
Exclude reactive thrombosis
Genetic testing
Characteristic bone marrow appearance
What might cause reactive thrombocythaemia?
Blood loss
Inflammation
Malignancy (particularly ovarian, GI)
Iron deficiency
