4.3 Chronic Myeloproliferative Disorders Flashcards
What is the term for too much red, ahite and platelets?
red: Polycythaemia
White: Leukocytosis
Platelets: Thombocytosis
What is the term for too little red, white and platelets
Red: Anaemia
White: Leucopenia
Platelets: Thrombocytopenia
Where do the genetic changes in CML occur?
Pluripotent stem cell
What is the common genetic abnormality in CML?
Translocation between chromosomes 9 (ABL) and 22 (BCR) leading to an increase in the ABL tyrosine kinase which is important in signal transduction and cell growth
What are the clinical features of CML?
Fatigue, weight loss, night sweats, splenomegaly, anaemia
What is used for the diagnosis of CML?
Changes on peripheral blood and BM biopsy
BCR-ABL translocation (cytogenetis)
What are the three phases of CML?
Chronic
Accelerated
Blast
What is the treatment of CML?
Tyrosine kinase inhibitor - Imatinib
Reduces the progression to accelerated phase or blast phase however some patients will develop mutations that reduce the effectiveness - new generation tyrosine inhibitors being used
What is polycythaemia vera?
Primary polycythaemia where there is an increase in RBC production independent of EPO
What are the clinical features of Polycythaemia vera?
Increased risk of arterial and venous thrombosis
Microcirculatory disorders - headaches, cisual disturbances, dizziness, erythromelagia
Hypertension
Plethora
Splenomegaly
What is the genetic mutation of polycythaemia vera?
Gain of function in Janus 2 kinase (JAK-2) which is the gene that encodes the tyrosine kinase a downstream regulator of EPO making cells hypersensitive to EPO
In which disorders will you see JAK2 mutations?
Polycythaemia vera
Essential thrombocytopenia
Primary idiopathic myelofibrosis
What is the diagnosis of polycythaemia vera?
Serum EPO suppressed
Identification of JAK2 mutation
Bone marrow biopsy: panmyelosis
What is the treatment of polycythaemia vera?
Venesection: reduces the blood volume and brings down the hematocrit levels; in patients with polycythemia vera, this reduces the risk of blood clots
Low dose aspirin
JAK2 inhibitors being developed
What is essential thrombocythaemia?
Chronic myeloproliferative neoplasm affecting the megakaryocytic lineage
What is the diagnosis of thrombocythaemia?
Sustained platelet count >450
Bone marrow: proliferation of megakaryocytes (no increase in erythropoiesis or granulopoiesis)
Doesn’t meet criteria for other myeloproliferative disease
JAK2 V617F nutation positive
What is the clinical presentation of thrombocythaemia?
Most aymptomatic but can show thrombosis or haemorrhage
What is the treatment of thrombocythaemia?
Hydroxyurea (affects all cell lines)
Anagrelide (megakaryocyte line - more side effects)
Low dose aspirin if high risk of vascular events
What is primary myelofibrosis?
proliferation of megakaryocytes and granulocytes in the bone marrow
In developed disease this is associated with reactive deposition of fibrosis connective tissue and extramedullary haematopoiesis
What are the clinical features of primary myelofibrosis?
30% asymptomatic - incidental splenomegaly or FBC abnormalaties
Can mimic essential thrombocytopenia
90% splenomegaly
50% hepatomegaly
Fatigue, dyspnoea, weight loss, night sweats, bleeding
What is the diagnosis of primary myelofibrosis?
Leukoerythroblastic on blood film
Bone marrow biopsy - proliferative, fibrotic phases
May have JAK2 or anothe rmutation
What is the clinical course of primary myelofibrosis?
As it progresses cytopenias develop Usually become transfusion dependent Ongoing splenic enlargement 3-7 year survival if diagnosed in fibrotic phase 5-30% transformation into AML
What is Nilotinib?
Tyrosine kinase inhibitor used for imatinib resistant CML
What is Ponatinib?
Kinase inhibitor targets at ABL-BCR used for CML and Ph+ ALL
Effective for CML resistant to imatinib
What is Ruxolitinib?
JAK 1 and 2 inhibitor for myelofibrosis
