Myeloproliferative Neoplasms and Myelodysplasia Flashcards
Common Myeloproliferative Neoplasms
- Chronic melogenous leukemia (CML)
- Polycythemia vera
- Primary myelofibrosis
- Essential thrombocythemia
Myeloproliferative Neoplasms General Symptoms
- Usually increased bone marrow cellularity
- Slightly increased marrow blasts (<10%)
- Normal morphology
- Effective hematopoiesis
- CBC- increased in one or more cell lines
- Organomegaly common; such as enlarged spleen
Tyrosine Kinases
- Enzyme that transfers phosphate group from ATP to a protein in a cell
- On/off switch for cellular function
- Disruption in the genes controlling these products lead to dysregulated/uncontrolled proliferation
Myeloproliferative Neoplasms Chart
Chronic Myelogenous Leukemia (CML)
- Prototypical myeloproliferative disorder
- Neutrophils w/ varying stages of maturation and increased basophils, hypercellular bone marrow w/ maturation of all cell lines; very little adipose tissue present in bone marrow as a result
- Most pts in 50-60’s
- Translocation b/w chromosome 9 to 22 (Philadelphia chromosome) = BCR-ABL fusion gene
- Most pts. diagnosed in chronic phase where white count is high but relatively stable
CML Chronic Phase
- Leukocytosis- median WBC count 100x 10^9/L (N is <10.8x 10^9/L), mainly neutrophils lineage
- Blasts usually <2% of WBCs
- Megakaryocytes small and hypolobated
CML Accelerated Phase Criteria
Any 1 or more of the following hematologic/cytogenetic criteria or response-to-TKI criteria:
- Persistent or increasing WBC (>10 x 10 ^9/L), unresponsive to therapy
- Persistent orincreasing splenomegaly, unresponsive to therapy
- Persistent thrombocytosis (>1000 x 10^9/L), unresponsive to therapy
- 10-19% blasts in the PB and/or BM
CML Blast Phase
- Evolving into acute leukemia (usually AML but can be ALL)
*blasts >20% of peripheral blood WBC or BM
CML Therapy
- Gleevec
*management of malignant clone; keep normal myeloid elements at sustainable level with reduced cytogenetic expression of fusion gene
*not a cure; can only work for so long
- Bone marrow transplant
*only potential curative option
Polycythemia Vera
- Increased RBC production independent of normal erythropoiesis
- Almost all have JAK2 mutation or variant thereof
- Increased red cell mass and panmyelosis
- Median survival is 13 years
Polycythemia Vera (PV) Symptoms
- Related to hypertension/vascular abnormalities due to increased red cell mass
*venous or arterial thrombosis
*myocardial infarction or stroke
*portal-splenic vein thrombosis/Budd-Chiari syndrome
Jak-2 Mutation
- Mutation is specific to myeloid neoplasms and confers proliferation advantage
Polycythemia Vera Diagnostic Criteria
- MAJOR:
*Hgb >16.5 g/dL for men; >16 g/dL for women (normal for men is ~13.5-17.0 g/dL, women 12.0 to 15.0 g/dL)
*presence of JAK2 mutation (no BCR-ABL1)
*no cause of secondary erythropoiesis (elevation of erythropoietin (EPO) due to hypoxia, high oxygen affinity Hb, EPO production by tumor)
- MINOR:
*BM hypercellularity w/ trilineage growth
*serum erythropoietin below reference range
*endogenous colony formation in vitro
- WHO PV criteria
*Hemoglobin >16.5 g/dL in men, >16.0 g/dL in women
*BM biopsy show hypercellularity for age w/ trilineage growth (panmyelosis) including prominent erythroid, granulocytic, and megakaryocytic proliferation w/ pleomorphic, mature megakaryocytes (diff. in size)
*presence of JAK2V617F or JAK2 exon 12 mutation
Polycythemia Vera 3 Phases
- Prodromal, prepolycythemic- only mild erythrocytosis
- Overt polycythemic- significantly increased RBC mass
- Spent phase- myeloproliferative and pancytopenia; extensive marrow fibrosis in spent phase (yellow/black stain for reticular fibers)
Budd-Chiari Syndrome
- PV is most common cause
- Thrombotic or non-thrombotic obstruction to hepatic venous outflow
- Hepatomegaly, ascites and abdominal pain = high mortalit (blood is able to get into liver but is hard to get out)
Primary Myelofibrosis (PMF)
- Proliferation of megakaryocytes w/ reticulin and collagen fibrosis
- Does not meet criteria for CML, PV, MDS or other
- Fibrotic marrow causes RBCs to become pear shaped, and leukoerythoblastosis = immature cells being forced into blood
Essential Thrombocythemia (ET)
- Platelet count >450 x 10^9/L
- Megakaryocytes proliferation w/ large and mature morphology
- HUGE, hyperlobated megakaryocytes easily distinguished from micro-megakaryocytes of CML
- Doesn’t meet criteria for CML, PV, PMF, MDS or other myeloid neoplasm
- Splenic or hepatic vein thrombosis
Elevated Tryptase Seen In
- Anaphylaxis and mastocytosis
Myelodysplasia/Myeloproliferative Disease
- Chronic myelomonocytic leukemia (CMML); not a ture leukemia
- Disease of older adults, incidence unknown
- Persistent peripheral blood monocytosis >1 x 10^9/L
- No Philadelphia chromosome
CMML to AML
- >20% blasts in blood/marrow
Juvenile Myelomonocytic Leukemia (JMML)
- Childhood version of CML
- Proliferation of granulocytic and monocytic lineages
- 10% of cases ass’d w/ neurofibromatosis type 1
- Diagnostic criteria: no Philadelphia chromosome
Neurofibromatosis-1
- 200-500-fold increased risk of developing myeloid malignancy
Myelodysplasia
- Group of clonal hematopoietic stem/multipotent cell disease
- Dysplasia and ineffective hematopoiesis of one or more myeloid cell lines
- can evolve into AML
- Usually increased bone marrow cellularity
- CBC w/ cytopenias; too few cell lineages
Ringed Sideroblasts
- Majority of iron entering RBCs is incorporated into heme
- Rest is stored as ferritin
- Always pathologic sign
