Myeloproliferative Neoplasms Flashcards
What are myeloproliferative neoplasms? What will the bone marrow look like? Who tends to get them?
Also called myeloproliferative disorders, they are clonal proliferations of hematopoietic stem cells leading to increased production of mature cells of the myeloid lineage, usually with one predominant cell type
Bone marrow appears hypercellular, tends to occur in older adults.
What happens to the CBC and liver/spleen in myeloproliferative neoplasms?
CBC shows elevated PMNs, RBCs, and platelets, but there will be one predominant elevated type depending on the disorder
Liver and spleen often show hepatosplenomegaly
What are the four important types of myeloproliferative neoplasms?
- Polycythemia Vera (PV)
- Essential Thrombocytopenia (ET)
- Chronic Myelogenous Leukemia (CML)
- Primary Myelofibrosis (MF)
What mutations are associated with each of the four main Myeloproliferative neoplasms?
- Polycythemia Vera (PV) - JAK2 always
- Essential Thrombocytopenia (ET) - JAK2 50%
- Primary Myelofibrosis (MF) - JAK2 50%
- Chronic Myelogenous Leukemia (CML) - philadelphia chromosome
What is polycythemia vera / what are the usual symptoms for a patient presenting? Why do they have these symptoms?
Disorder of increased RBCs due to Jak-2 mutation, primary polycythemia
Usually asymptomatic, but often has headaches, visual disturbances, and dizziness due to increased blood viscosity
What are some other symptoms other than neurological which can present due to high hematocrit in polycythemia vera?
Venous / portal thrombosis, arterial thrombosis
What are the rarer but classic symptoms of polycythemia vera?
- Intense pruritis (itching) following a shower due to increased mast cells (WBCs can also go up in this condition)
- Erythromelalgia - pain and red-blue discoloration in hands and feet
What is seen on bone marrow smear of PV?
Hypercellular bone marrow, with erythroid and megakaryocytic hyperplasia
How does PV differ from secondary polycythemia?
Erythropoietin levels will be decreased -> stem cells are proliferating without growth signal
Secondary polycythemia is a reactive process
Including polycythemia vera, what, in general, can myeloproliferative disorders ultimately progress to?
Marrow fibrosis w/cytopenias, or acute leukemia
What is the treatment for polycythemia vera?
- Phlebotomy - to reduce hyperviscosity
2. Hydroxyurea - a ribonucleotide reductase inhibitor (chemotherapy)
What are some causes of secondary polycythemia? One of these is a pseudopolycythemia.
- High EPO levels
- Chronic hypoxemia in smokers
- Lung disease
- High altitudes
- Severe dehydration - reduced plasma volume makes a relatively increased hemoglobin
What are the criteria for essential thrombocytopenia? This includes bone marrow biopsy and mutations.
Chronic elevated non-reactive platelet count (>450k) not accounted for by other MPNs
Bone marrow biopsy showing mainly megakaryocytes, especially with hyperlobulated nuclei
Absence of a philadelphia chromosome, and presence of a characteristic mutation (i.e. JAK2)
What are classical symptoms of essential thrombocytopenia?
Usually asymptomatic, but may present with bleeding and thrombosis events, headache, lightheadedness, syncope
What will peripheral blood smear and bone marrow show for ET?
Peripheral smear - greater than 10 platelets per high power field
Bone marrow - Megakaryocytic proliferation had to distinguish from P Vera
What are the treatments for ET? What can it progress to?
Aspirin (platelets) and hydroxyurea
Can progress to myelofibrosis and AML, much like all other myeloproliferative syndromes
What is primary myelofibrosis (PMF)? Give the pathophys
Chronic proliferation of myeloid stem cells in marrow leads to progressive reactive fibrosis of bone marrow
-> due to PDGF from megakaryocytes especially stimulating fibroblasts to cause fibrosis
What systemic symptoms are likely to develop in primary myelofibrosis and why?
- Massive hepatosplenomegaly due to extramedullary hematopoesis in liver and spleen since there’s no room in bone marrow to do this anymore
- Hypermetabolic state due to cytokines secreted by platelets, leading to fever, bone pain, and night sweats
- Anemia is also common
What does the peripheral blood smear show for PMF? Why?
Leukoerythroblastic smear - spleen is not built to hold all these hematopoesis so immature cells leak out
Includes “tear drop RBCs”, nucleated RBCs, and immature neutrophils
What is the prognosis and treatment for PMF?
Way worse than PV and ET, median survival is 3-5 years and will need bone marrow transplant.
If untreated, often progresses to AML
What is the most common myeloproliferative neoplasm and explain the mutation associated with it?
Chronic Myelogenous Leukemia
- > driven by 9;22 translocation, philadelphia chromosome (think of Liberty Bell in sketchy)
- > ABL gene (encoding a tyrosine kinase) on chromosome 9 is translocated into BCR (breakpoint cluster region) on chromosome 22, leading to constitutive expression
What are the features of CML on peripheral smear and bone marrow CML?
Uncontrolled production of granulocytes: think of red, white and blue pebbles in sketchy (think eosinophils, neutrophils, and basophils which are characteristically increased)
-also has increased immature cells, high platelet counts, and anemia. Bone marrow is hypercellular
What are the phases of CML infection and when are most patients diagnosed?
Chronic phase - most patients diagnosed here by CBC when asymptomatic
Accelerated phase - increased output of mature myeloid cells, marked by enlargement of the spleen
Terminal blast crisis - right before it becomes an acute leukemia
What does CML progress to?
AML in 2/3 of cases and ALL in 1/3 of cases
What is used to treat CML?
- > treated by a imatinib - guy imitating painting in sketchy. Nib of Benjamin Franklin’s pen.
- > tyrosine kinase inhibitor
What other malignancy displays the philadelphia chromosome and how can it be distinguished from CML?
De novo ALL (acute lymphoblastic leukemia not preceded by CML)
ALL has a 190kD fusion protein, whereas CML has a 210kD fusion protein
What are three ways that CML can be told from a normal leukemoid reaction (reactive neutrophilic leukocytosis)?
CML:
- Leukocyte alkaline phosphatase (LAP) negative. LAP+ = neutrophils made to fight infection, more well developed than CML
- Increased basophil count (absent in leukemoid)
- Philadelphia chromosome
