Myeloproliferative Neoplasms Flashcards
Overproduction of RBCs
Primary defect of Polycythemia vera
Overproduction of granulocytes
Primary defect of chronic myelocytic leukemia
Overproduction of platelets
Primary defect of Essential Thrombocytosis
Overproduction of bone marrow fibroblasts
Primary defect of Primary Myelofibrosis
Can exhibit hypereosinophilia and/or hyperbasophilia
myeloproliferative neoplasms (MPNs)
Best known mutation is in the gene for a protein called JAK2 (>90%)
Polycythemia vera
All cells appear normal
RBCs function normally and have normal lifespan
Polycythemia Vera (PV)
Stem cells with JAK2 mutation are resistant to erythropoietin apoptosis
Polycythemia Vera (PV)
- Hgb level
- Identification of JAK2 mutation
Major criteria of PV
(both need to be met)
- Panmyelosis in bone marrow
- Low serum EPO level
- Autonomous, erythroid colony formation
Minor criterion of PV (only 1 needs to be met)
18.5 g/dL in men
16.5 g/dL in women
PV Hgb levels for major criteria
Low EPO levels
PV lab findings
Anemia
Fever
Excessive bleeding or bruising
Malaise
Hepatosplenomegaly
CML Clinical Symptoms
- Causes extreme elevation of both mature & immature myeloid cells in bone marrow which then shows up in the p.b.
- Slow clinical course
- Primarily seen in adults, but can occur at any age
CML
> 95% patients are Philadelphia (Ph’) chromosome +
CML Cytogenetics
BCR/ABL fusion protein
CML Cytogenetics
When the p.b. Looks like bone marrow!
CML lab findings
P.b. shows a huge left shift with all developmental stages!
CML lab findings
> 20% basophilia heralds an impending blast crisis
CML lab findings
- chronic phase
- accelerated phase
- blastic phase
Three phases of CML
- Usually occurs prior to blastic phase
- Poor response to therapies
- Increase in symptoms and lab values
Accelerated phase of CML
- About ¾ CML patients undergo “blast transformation” from chronic into acute phase
- Increased blast count to >20%
- Becomes either AML, or more rarely, ALL
Blastic phase of CML
________ binds directly to the BCR/ABL fusion protein/tyrosine kinase produced by Ph’
Gleevec
And eventually no more abnormal, Ph translocation-containing cells can be found = _____ ______
Molecular Remission - Treatment with Gleevec
It cures > 88% of patients in chronic phase (with variable results in other phases)
Treatment with Gleevec
Clonal stem cell disorder (Associated w/ JAK2 mutation- 65% of patients)
Primary Myelofibrosis (PMF)
Aka. Chronic Idiopathic Myelofibrosis (CIMF) and myelofibrosis with myeloid metaplasia, MMM
Primary Myelofibrosis (PMF)
Dry tap due to varying degrees of bone marrow fibrosis
Primary Myelofibrosis (PMF)
Patients usually die from 2 most common complications of bone marrow failure ?
Overwhelming infections & massive hemorrhage – Primary Myelofibrosis
Clonal stem cell disorder (associated with JAK2 mutation)
Causes extremely ↑ platelet count
Essential Thrombocythemia
Platelet function is abnormal unless numbers ↓ by plateletpheresis – this differentiates ET from what leukemia?
AML M7 – AMegL
- Platelet count ~600,000- 2,500,00/uL
- Giant bizarre plts., but not megakaryocyte fragments in p.b.
- Slt. leukocytosis with neutrophilia
- Abnormal plt. Aggregation studies
Essential Thrombocythemia
- Positive Giant Platelets
- NO nRBCs
- Slight left shift
- No megakaryocyte fragments
Essential Thrombocythemia
- Positive Giant Platelets
- Positive nRBCs
- Rare left shift
- Positive megakaryocyte fragements
M7 (AMegL)
