Myeloproliferative neoplasms Flashcards
Types of myeloproliferative neoplasms
Chronic myeloid leukemia (CML)
Polycythemia vera
Essential thrombocythemia
Primary myelofibrosis
Myeloproliferative neoplasm associated with Philadelphia chromosome
CML
Translocation associated with CML
t(9;22)(q34;q11)
BCR-ABL
truncated chromosome 22
Ph chromosome
Routinely used for monitoring response to therapy in CML
RT-PCR
Generally age of CML
40-60 years
Common symptoms of CML
Mild to moderate anemia
Weight loss and anorexia
Splenomegaly
Less common symptoms of CML
Hyperuricemia –> gout
Platelet dysfunction –> bruising and bleeding
Three phases of CML
Chronic phase
Accelerated phase
Blast crisis
Increasing spleen size and/or resistance to therapy in CML
Blast crisis
Progression of blast crisis in CML
70% develop AML
30% develop B cell ALL
Characteristics of accelerated phase of CML
Increasing basophils
Thrombocytopenia
Myeloblasts
Characteristics of peripheral smear in CML
High WBC with immature neutrophils beyond blast cell stage
Characteristics of bone marrow histology in CML
Hypercellular
Increased granulocytic precursors, eosinophils, and megakaryocytes with micromegakaryocytes
Mutation in polycythemia vera
Point mutation in JAK2
Blood characteristics in polycythemia vera
Increased RBC mass
HCT >60%
Increased Hgb
Hyperviscosity and hypervolemia
Pt presentation in polycythemia vera
HA
Dizziness
HTN
Blurred vision
Plethoric and cyanotic
Splenomegaly
Marrow biopsy in polycythemia vera
Hypercellular
Panmyelosis
Increased megakaryocytes with frequent hyperlobated forms
Possible progression of polycythemia vera
Myelofibrosis (30%)
AML (5%)
Activating point mutations in essential thrombocythemia
JAK2 (50-60%)
CALR (30%)
MPL (5-10%)
Causes of reactive thrombocytosis
Bleeding
Inflammatory disorders
Iron deficiency
Clinical features of essential thrombocythemia
Older age
Thrombotic complications
Gangrene
Erythromelalgia
Blood smear in essential thombocythemia
Increased platelets
Abnormally large platelets
Peripheral smear in primary myelofibrosis
Tear drop cells/dacrocytes
Variable immature myeloid cells
Nucleated RBCs
Marrow biopsy in primary myelofibrosis and stain
H&E stain
Extensive fibrosis with collagen fibers
Mutations associated with primary myelofibrosis
Activating JAK2, CALR, or MPL
Pathogenesis of primary myelofibrosis
Increased secretion of TGF-beta from marrow cells leads to fibrosis
Possible progression of primary myelofibrosis
AML (10-20%)
Clonal disorders of hematopoietic stem cells
Myelodysplastic syndromes
Clinical features of myelodysplastic syndromes
Refractory anemia
Infections
Abnormal bleeding manifestations
Neutrophil changes in myelodysplastic syndromes
Abnormal nuclear chromatin condensation
Pseudo-Pelger-Huet cells - bilobed nuclei
Hypo-granularity
Erythroid cell changes in myelodysplastic syndromes
Megaloblastic change
Dyserythropoiesis
Ringed sideroblasts
Megakaryocyte changes in myelodysplastic syndromes
Micromegakaryocytes with single hypolobated nuclei
Megakaryocytes with multiple separated nuclei
Cytogenic abnormalities in myelodysplastic syndrome
Monosomies 5 and 7
-5q
-7q
-20q
+8
Outcomes of myelodysplastic syndromes
Transform to AML
Medial survival of 9-29 months
