27. Myeloid proliferative disorders Flashcards
What type of genes are implicated in MPNs?
What do mutations in these genes cause?
Genes involving protein tyrosine kinases
Cause constitutively active signal transduction - leads to abnormal proliferation
How are MPNs characterised?
Normal maturation but increased proliferation of mature cells
What type of cells accumulate in MPNs?
Usually mature cells of the myeloid lineage
Erythrocytes, granulocytes, platelets
What is PV and what cells proliferate?
Polycythaemia vera
Primarily erythrocytes, - caused raised HB
Also granulocytes and megakaryocytes
What is the clinical phenotype of PV?
Hypertension, hepatosplenomegaly, fatigue, dizziness
Shortened life expectancy
What is the risk of progression in PV?
20% transform to AML/MDS
What is ET and what cells proliferate?
Essential thrombocythaemia
Megakaryocytic lineage - Platelets
What is the clinical phenotype of ET?
Headaches, dizziness, syncope, splenomegaly, thrombosis
Near normal life expectancy
What is the risk of progression in ET?
9% risk of progression to MF, 2% to AML/MDS
What is MF and what cells proliferate?
Primary myelofibrosis
Megakaryocytes and granulocytes - cause deposits of fibrous connective tissue in BM
What is the clinical phenotype of MF?
Organomegaly, anaemia, bleeding episodes
Pancytopenia and extramedullary haematopoiesis
Median survival <3 years
What is the risk of progression in MF?
10-20% risk of progression to AML
How is MF characterised morphologically?
Nucleated, teardrop-shaped RBCs
Large platelets
Increased CD34+ blasts
What genes are involved in MPNs
JAK2 V617F or ex12 in 50% of PV cases and 50% of ET/MF
ET and MF also CALR frameshifts, MPL ex10
How does the JAK/STAT pathway function normally?
JAK2 = Non-receptor tyrosine kinase
Receptor causes phosphorylation of JAK2 > phosphorylates STAT and MAPK > DNA transcription > cell proliferation
