Myeloproliferative diseases Flashcards
What are the myeloproliferative diseases?
- Polycythaemia Vera
- Essential Thrombocythaemia
- Primary Myelofibrosis
What does the term myeloproliferative disease mean?
Describes a group of conditions arising from marrow stem cells of the myeloid progenitors.
What is the predominant cause of these disorders.
An aquired Mutation which affects the JAK2 signalling mechanism. JAK2 V617F, JAK2 exon12
What is the predominant mutation?
Val @ 617 replaced by Phe. This mutation occurs in 90-97% of patients with PV and 50% of patients with ET and Primary Myelofibrosis.
What is the role of JAK2?
Plays a major role in tranducing signals from proliferative molecules such as IL-3, EPO, GM-CSF, G-CSF and TPO.
What is Polycythemia?
An increase in the haemoglobin concentration above the upper limit for the patients age and sex.
What is Polycythemia Vera?
Is the increase in red cell volume caused by a clonal malignancy of a marrow stem cell. The stem cell through a mutation receives a proliferative advantage.
What are some accompanying signs in PV?
- Pancytosis (over production of granulocytes and and platelets)
- Blurry vision and headache
- Increased risk of venous thrombosis (e.g hepatic vein, portal vein, and dural sinus)
- Flushed face due to congestion
- Itching especially after a bath due to histamine release from increased mast cells
- Hepatosplenomegaly
What are signs of Myeloproliferative disorder?
- Late adult onset 50-60
- High WBC count and hypercellular marrow
- Increased risk of hyperuricemia and Gout due to high cell turnover
- Risk of progression to marrow fibrosis or transformation to acute Leukemia
What is the etiology of PV?
JAK2 mutation on Chromosome 9 short arm which result in hypersensitivity to growth factors.
How is PV different from reactive/secondary Polycythemia?
- In PV EPO LEVELS are low and Sao2 is normal
- In secondary polycythemia due to high altitude or renal cell carcinoma EPO is high
- In reactive polycythemia due to high altitude or lung disease Sao2
