SM_263b: Myeloproliferative Disorders and CML Flashcards
(41 cards)
Myeloproliferative disorders are ____, ____, ____, and ____
Myeloproliferative disorders are essential thrombocythemia, polycythemia vera, primary myelofibrosis, and chronic myeloid leukemia
- Stem cell diseases
- Thrombotic and hemorrhagic complications
- Extramedullary hematopoiesis
- Marrow fibrosis
- Leukemic transformation
Philadelphia chromosome is present in ____ and creates ____
Philadelphia chromosome is present in CML and creates a fusion gene coding for a protein with tyrosine kinase activity that promotes proliferation and prohibits apoptosis
t(9;22) creates a ___ with a ___
t(9;22) creates a Philadelphia chromosome with BCR-ABL fusion gene
____ is present in most people with myeloproliferative disorders
JAK2 V617F is present in most people with myeloproliferative disorders
- Substitution of valine to phenylalanine at codon 617
Describe pathogenesis of JAK2 mutation
JAK2 mutation
- JAK2 mutation
- JAK2 activates 3 main myeloid cytokine receptors: erythropoietin receptor, thrombopoietin receptor, and G-CSG receptor
Mutations can be heterozygous or homozygous (mitotic recombination)
TPO activates ___ then ___
TPO activates MPL than JAK2
MPL mutations ___
MPL mutations activate receptor in absence of ligand (TPO)
- Most frequent types: W515L and located on transmembrane and cytosolic domains of MPL
- Mutations typically heterozygous
Wild-type CALR is an ___
Wild-type CALR is an ER chaperone involved in quality control of proteins and calcium storage
Describe CALR pathogenesis
CALR pathogenesis
- Heterozygous mutations
- Type 1: 52 bp deletion, type 2: 5 bp insertion
- CALR mutations activate MPL receptor
Polychthemia vera is associated with molecular defects in ___ and ___
Polychthemia vera is associated with molecular defects in JAK2 V617F and JAK2 exon 12
Essential thrombocytosis is associated with molecular defects in ___, ___, and ___
Essential thrombocytosis is associated with molecular defects in JAK2 V617F, CALR, and MPL
Primary myelofibrosis is associated with molecular defects in ___, ___, and ___
Primary myelofibrosis is associated with molecular defects in JAK2 V617F, CALR, and MPL
Chronic myeloid leukemia is associated with molecular defects in ___
Chronic myeloid leukemia is associated with molecular defects in BCR-ABL
Describe essential thrombocythemia
Essential thrombocythemia
- Persistent thrombocytosis (> 450 * 109/L)
- Bone marrow with proliferating megakaryocytes: increased enlarged mature megakaryocytes
- Not meeting WHO criteria for another chronic myeloid neoplasms
- Demonstration of a clonal marker (JAK2, CALR, MPL) or no evidence of reactive thrombocytosis in evidence of clonal marker
Describe peripheral blood findings of essential thrombocythemia
Essential thrombocythemia peripheral blood
- Thrombocytosis: often marked, small to giant platelets
- Minimal to no leukocytosis
- Mild anemia but usually normal Hb
Describe bone marrow findings of essential thrombocythemia
Essential thrombocythemia bone marrow
- Normocellular to hypercellular
- Increase in megakaryocytes: large to giant, abundant cytoplasm, hyperlobulated nuclei
- Reticulin (fibrosis) and iron stains usually normal
Describe essential thrombocythemia clinical presentation
Essential thrombocythemia clinical presentation
- Microvascular disturbance (usually due to platelet hypersensitivity): headache, TIA, dizziness, visual disturbance, erythromelalgia
- Macrovascular disturbance (older age, leukocytosis, JAK2 V617F, prior thrombosis): stroke, ACS, DVT/PE, abdominal vein thrombosis
Describe the mutational profile of essential thrombocythemia
Essential thrombocythemia mutational profile
Compare true essential thrombocythemia with prefibrotic myelofibrosis
True essential thrombocythemia with prefibrotic myelofibrosis
Describe management of essential thrombocythemia
Essential thrombocythemia
- Manage CV risk factors
- Aspirin
- Cytoreduction indicated for high risk (> 60 with JAK2+ or thrombosis history)
Describe diagnosis of polycythemia vera
Polycythemia vera diagnosis
Major
- Hgb > 16.5 g/dL in men (or Hct > 49%), > 16.0 g/dL in women (Hct > 48%)
- Bone marrow biopsy showing hypercellularity for age with prominent erythroid, granulocytic, and pleomorphic megakaryocytic proliferation
- Presence of JAK2 V617F or JAK2 exon 12 mutation
Minor
- Subnormal Epo level
Describe bone marrow findings in polycythemia vera
Polycythemia vera bone marrow findings
- Hypercellularity and tri-lineage proliferation, particularly of megakaryocytes
- Sustainable iron usually absent
- Occassional fibrosis, even at diagnosis
Describe clinical presentation of polycythemia vera
Polycythemia vera clinical presentation
- Microvascular disturbance (usually due to platelet hypersensitivity): headache, TIA, dizziness, visual disturbance, erythromelalgia
- Macrovascular disturbance (older age, leukocytosis, JAK2 V617F, prior thrombosis): stroke, ACS, DVT/PE, abdominal vein thrombosis
___, ___, and ___ are additional complications of polycythemia vera
Aquagenic pruritis, gout, and bleeding are additional complications of polycythemia vera
- Aquagenic pruritis: increased histamine levels
- Gout: increased uric acid
- Bleeding: acquired von Willebrand’s disease
