Myeloproliferative Disorders
Myeloproliferative disorders are stem cell disorders that that result in excess production and overaccumulation of erythrocytes, granulocytes, and/or platelets. These abnormalities may appear in bone marrow, peripheral blood, and body tissues.
The main types include:
- Chronic myelogenous leukemia (CML)
- Polycythemia vera (PV)
- Essential thrombocythemia (ET)
- Primary myelofibrosis (PMF)
Condition | Cause | Lab Findings | Diagnostic Tests | Treatment | |
---|---|---|---|---|---|
Peripheral Blood | Bone Marrow | ||||
Chronic Myelogenous Leukemia | t(9,22)
|
|
|
|
|
Polycythemia Vera | JAK2 mutation (V617F)
|
|
|
|
|
Essential Thrombocythemia | JAK2, CALR, or MPL mutation |
|
|
Must not match any other MPD criteria or be caused by reactive thrombocytosis
|
|
Primary Myelofibrosis | JAK2 (60%)
|
|
|
Must not match any other MPD criteria
|
|
General Features
- Tend to affect adult and geriatric populations
- Begin as chronic disorders, which may transform into subacute, and then acute disorders
- Subacute
- Acute: aggressive growth (acute myeloid leukemia)
- May cause marrow hypoplasia/depletion of cells
- Common lab features:
- Splenomegaly (60-100%)
- Cytogenetic abnormalities
Chronic Myelogenous Leukemia
- caused by translocation of genes in pluripotent hematopoietic stem cells
- Philadelphia chromosome (Ph) in >90% of leukemic cells
- reciprocal translocation between chromosomes 9 and 22. t(9,22)
- BCR/ABL fusion proteins affect tyrosine kinase activity
- Unregulated cell growth, failure to undergo apoptosis
- clonal overproduction of myeloid cell line
- increased immature neutrophils
- Has 3 phases:
- Chronic: <10% blasts
- Accelerated: 10-19% blasts, basophilia in peripheral blood
- Acute: >20% blasts
- Lab findings:
- Peripheral Blood:
- Neutrophilia, with all phases of maturation
- Leukocytosis
- Left shift (promyelocytes and blasts)
- Basophilia
- Eosinophilia
- Thrombocytosis
- Neutrophilia, with all phases of maturation
- Bone Marrow:
- Myeloid hyperplasia
- Hypercellularity
- M:E ratio increased (10:1)
- Chemistry
- ↑ uric acid (due to ↑ cell turnover)
- ↑ lactate dehydrogenase
- ↑ serum B12 (due to ↑ breakdown of WBCs)
- Peripheral Blood:
Polycythemia Vera
- Caused by substitution in JAK2 gene (90-97% caused by V617F)
- Mutated protein is active without requiring erythropoietin
- Upregulation of anti-apoptotic protein
- Cell divides normally but doesn't undergo apoptosis
- Signs and Symptoms:
- Ruddy cyanosis (reddish-purple colour to face)
- Vascular complications
- Splenomegaly
- Lab Findings:
- Peripheral Blood:
- Absolute erythrocytosis
- ↑ HGB, HCT
- IDA may develop
- Moderate leukocytosis and thrombocytosis
- Peripheral Blood:
Essential Thrombocythemia
- Marked thrombocytosis >450x10^9L
- Large masses of platelet aggregates
- Abnormal platelet morphology
- Giant platelets, megakaryocyte fragments
- Possibly ↑ WBC (neutrophilia with slight left shift)
- Lab Findings:
- Abnormal coagulation studies
- Abnormal platelet aggregation
- BM: Megakaryopoiesis (large, mature megakaryocytes with no other increases in cell types)
- Genetics
- JAK2, CALR, or MPL mutations
- Abnormal coagulation studies
Primary Myelofibrosis
- Abnormal megakaryocyte growth stimulates collagen production by BM fibroblasts
- JAK2 V617F associated with 60% of cases
- Fibrinoblastic growth factors support collagen production
- BM tissue is replaced with fibrous materials, causing fibrosis
- BM failure develops are cellularity is lost
- Extramedullary hematopoiesis
- Infiltration of BM with fibrous materials results in stem cells being push out into other tissue
- Hematopoiesis begins occurring outside of BM
- Accumulation of cells in spleen, liver, and other organs
- Can cause fibrosis of other organs (e.g., spleen)
- anemia, thrombocytopenia
- Lab Results:
- Bone Marrow
- "Dry tap" where no aspirate is collected
- BM biopsy showing fibrosis in >1/3 of biopsy section
- Bone Marrow
- Myelofibrosis
- Increased fine fibres (reticulin, type III collagen)
- Myelosclerosis
- increased coarse, type I collagen
- Treatment
- Stem cell transplants
- Splenectomy
- Chemotherapy
- JAK2 inhibitors