Haem: CML and myeloproliferative disorders Pt.2 Flashcards
What is primary myelofibrosis?
- A clonal myeloproliferative disease associated with reactive bone marrow fibrosis
- Characterised by extramedullary haemopoeisis
- NOTE: other myeloproliferative disorders can transform into myelofibrosis
Outline the typical presentation of primary myelofibrosis.
- Cytopaenias (anaemia, thrombocytopaenia)
- Thrombosis
- MASSIVE splenomegaly
- Hepatomegaly
- Hypermetabolic state (FLAWS)
What might you expect to see in the blood film of a patient with primary myelofibrosis?
- Leucoerythroblastic picture
- Tear drop poikilocytes (Dacrocytes)
- Giant platelets
- Circulating megakaryocytes
What is a characteristic feature seen on bone marrow aspirate in primary myelofibrosis?
Dry tap
What might you see on histological analysis of a trephine biopsy in primary myelofibrosis?
- Increased reticulin and collagen fibrosis
- Prominent megakaryocyte hyperplasia and clustering
- New bone formation
Which mutations would you test for in a patient with primary myelofibrosis?
JAK2 and Calreticulin
NOTE: these are not diagnostic
What are some bad prognostic features in primary myelofibrosis?
- Severe anaemia
- Thrombocytopaenia
- Massive splenomegaly
NOTE: median survival is 3-5 years
Outline the treatment options for primary myelofibrosis.
- Supportive - RBC and platelet transfusions (usually ineffective becasue of splenomegaly)
- Hydroxycarbamide (may worsen anaemia)
- Ruxolitinib - JAK2 inhibitor
- Allogeneic stem cell transplantation
- Splenectomy - dangerous operation but may provide symptomatic relief
What might you expect to see in the FBC of a patient with CML?
- Leucocytosis (MASSIVE)
- Normal or raised Hb and platelets
What would you expect to see in abundance in the blood film of a patient with CML?
- Neutrophils
- Basophils
- Myelocytes (NOT blasts)
NOTE: myelocytes are immature myeloid cells that are NOT blasts (analogous to reticulocytes for red blood cells)
Briefly describe the natural history of CML before targeted treatment was available.
- 5-6 years stable phase
- 6-12 months accelerated phase
- 3-6 months blasst crisis
What is the Philadelphia chromosome?
CML is caused by a translocation between 9;22 producing a derivative chromosome, 22q, which is called the Philadelphia chromosome
What are the two genes that make up the fusion gene in the Philadelphia chromosome?
Bcr = breakpoint cluster region
Abl = ableson tyrosine kinase
Explain how the Philedelphia fusion gene results in excessive proliferation of myeloid cells.
- Abl is a tyrosine kinase that drives cell proliferation but is rarely expressed unless the cells are receiving a stimulus to proliferation
- Bcr is a housekeeping gene that is constitutively active
- The Bcr-Abl fusion gene means that the tyrosine kinase component is constitutively activated thereby driving cell proliferation in the absence of a stimulus
List some diagnostic techniques used to identify CML and monitor response to treatment.
- FBC and leucocyte count
- Cytogenetics and detection of Philadelphia chromosome (FISH)
- RT-PCR to detect and quantify the number of copies of Bcr-Abl fusion transcript
NOTE: RT-PCR transcript % is the most sensitive
