William Dameshek in 1951 first described the term chronic myeloproliferative disorder. It encompassed four entities that were clinically separate. These included:
- Chronic myelogenous or myeloid leukemia (CML)
- Polycythemia Vera (PV)
- Essential Thrombocytosis (ET)
- Chronic Idiopathic Myelofibrosis (CIMF)
It was in 2001 that the World Health Organization added several entities to this list including:
- Chronic Neutrophilic Leukemia (CNL)
- Chronic Eosinophilic Leukemia (CEL)
- CEL/Hypereosinophilic Syndrome
- Chronic Myeloproliferative Disorder, Unclassified
This list was further modified in 2008 by the WHO. The WHO then changed the terminology from “myeloproliferative disease” to “myeloproliferative neoplasm”. In addition they added Mastocytosis to this new category.
The diagnostic criteria were also altered from the 2001 report. The new categories included:
- Myeloproliferative Neoplasms (MPN)
- CML, BCR-ABL1 positive
- Chronic Neutrophilic Leukemia CNL
- Polycythemia Vera (PV)
- Primary Myelofibrosis (formerly CIMF)
- Essential Thrombocytosis ET
- Chronic Eosinophilic Leukemia CEL, Not Otherwise Specified (NOS)
- Cutaneous Mastocytosis
- Systemic Mastocytosis
- Mast Cell Leukemia
- Mast Cell Sarcoma
- Extracutaneous Mastocytoma
- Myeloproliferative Neoplasms MPN, Unclassifiable
- Myeloid and lymphoid neoplasms associated with eosinophilia and abnormalities of PDGFRA, PDGRRB or FGFR1
- Myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
- Chronic myelomonocytic leukemia (CMML)
- Juvenile myelomonocytic leukemia (JMML)
- Atypical chronic myeloid leukemia, BCR–ABL-negative (aCML)
- Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-t)
- Myelodysplastic syndrome (MDS)
Diagnosis of MPN
For diagnosis of MPN the criteria include:
- CML: BCR-ABL1
- The BCR-ABL1 negative MPN
- PV with genetic mutations of JAK2 V617F, or JAK2 exon 12
- ET with genetic mutations of JAK2 V617F, or MPL W515L/K
- PMF with genetic mutations of JAK2 V617F, or MPL W515L/K
- Mastocytosis with genetic mutations of KIT D816V
For clinical diagnosis
- In CML the White blood cell (WBC) count usually is around 100,000, with absolute basophilia, and <2% myeloblasts; with variable hemoglobin and platelet levels
- In Polycythemia Vera hemoglobin usually 19-20 gm/dL and WBC count usually less than 20-30,000, and normal to slightly elevated platelet count
- In Essential Thrombocytosis platelet count usually more 1,000,000 WBC count usually less than 20-30,000, and normal to low hemoglobin level
Bone marrow examination:
- In CML there is granulocytic hyperplasia. Cells are absent-to-minimal in early (Chronic Phase) disease and are increased in late stages.
- In PV there is erythroid hyperplasia or excessive growth of the RBC precursors. Cells are absent-to-minimal in early disease and are increased in late stages.
- In ET megakaryocytic hyperplasia or excessive growth of the platelet precursors.
- In MPN there is fibrosis
- In mastocytosis there are mast cell infiltrates. The cells form loosely scattered nest like formations
- In CML 90-95% of cases will have the characteristic translocation at chromosomes 9 and 22 called the Philadelphia Chromosome t(9:22). -10% of cases will have a variant translocation or a cryptic translocation of 9 and 22.
- In PV more than 95% of patients with have a point mutation in the Janus Kinase2 gene (JAK2)—V617F or at JAK2 exon 12 mutations. JAK2 kinase is a member of a family of tyrosine kinases.
- In ET 40-50% of patients have the JAK2 V617F mutation. 1% will have a mutation in MPL—MPL W515K/L
- In Mastocytosis more than 95% will have a mutation at the D816V, within the KIT tyrosine kinase gene.
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)