The field of myeloproliferative disorders (MPDs) has evolved considerably since the sentinel observations made by William Dameshek in 1951. He had commented in an editorial in the journal Blood: "To put together such apparently dissimilar diseases as chronic granulocytic leukemia, polycythemia, myeloid metaplasia and di Guglielmo's syndrome may conceivably be without foundation, but for the moment at least, this may prove useful and even productive. What more can one ask of a theory?" (1).
The central feature among the MPDs is effective clonal myeloproliferation without dysplasia. Other features shared by most MPDs include involvement of a multipotent hematopoietic progenitor cell, marrow hypercellularity, predisposition to thrombosis, hemorrhage, and marrow fibrosis, and more recently, mutations in different tyrosine kinases (TK), for example, JAK2 (Janus kinase 2), platelet-derived growth factor receptor (PDGFR), and KIT (2–5). When the concept of MPDs was first proposed, it consisted of five disorders: chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), chronic idiopathic myelofibrosis (CIMF), and erythroleukemia. Over the years, erythroleukemia was reclassified under acute myeloid leukemia (AML). The remaining four (CML, PV, ET, CIMF) are recognized as classic MPDs.
The World Health Organization (WHO) 2001 classification assigned the classic MPDs to a broader category of chronic MPDs that also included atypical MPDs, namely, chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES), and chronic MPD, unclassifiable (MPD-U). The MPDs were, in turn, classified among one of the five categories of myeloid neoplasms, the others being: (1) AML, (2) myelodysplastic syndromes (MDS), (3) MDS/MPD, and (4) mast cell disease (MCD).
In the revised 2008 WHO classification system for chronic myeloid neoplasms, the phrase disease in both MPD and MDS/MPD has been replaced by neoplasm, reflecting the neoplastic nature of these conditions, so that MPD is now referred to as myeloproliferative neoplasm (MPN) (6). In addition, MCD is now included within the MPN category (Table 6-1). Also, CIMF has recently been renamed as primary myelofibrosis (PMF). CML, characterized by the reciprocal translocation of chromosomes 9 and 22, is discussed in detail elsewhere. Here we discuss classic MPNs, as well as CEL/HES and MCD, for which important advances have been made, both in the understanding of the disease pathology and clinical management.
Table 6–1. The 2008 World Health Organization Classification Scheme for Myeloid Neoplasms |Favorite Table|Download (.pdf)
Table 6–1. The 2008 World Health Organization Classification Scheme for Myeloid Neoplasms
|1. Acute myeloid leukemia|
|2. Myelodysplastic syndromes (MDS)|
|3. Myeloproliferative neoplasms (MPN)|
|3.1 Chronic myelogenous leukemia|
|3.2 Polycythemia vera|
|3.3 Essential thrombocythemia|
|3.4 Primary myelofibrosis|
|3.5 Chronic neutrophilic leukemia|
|3.6 Chronic eosinophilic leukemia, not otherwise categorized|
|3.7 Hypereosinophilic syndrome|
|3.8 Mast cell disease|
|3.9 MPNs, unclassifiable|
|4.1 Chronic myelomonocytic leukemia|
|4.2 Juvenile myelomonocytic leukemia|
|4.3 Atypical chronic myeloid leukemia|
|4.4 MDS/MPN, unclassifiable|
|5. Myeloid neoplasms associated with eosinophilia and abnormalities of PDGFRA, PDGFRB, ...|