myeloproliferative neoplasms

/WP/

Definition: The myeloproliferative diseases (MPDs) or myeloproliferative neoplasms (MPNs) are a group of diseases of the bone marrow in which excess cells are produced.

The myeloproliferative diseases (MPDs) are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than these conditions.

The concept of "myeloproliferative disease" was first proposed in 1951 by the eminent hematologist William Dameshek. In the most recent World Health Organization classification of Hematologic malignancies, this group of diseases was renamed from "myeloproliferative diseases" to "myeloproliferative neoplasms". This reflects the underlying clonal genetic changes that are a salient feature of this group of disease.

Although not a malignant neoplasm like other cancers, MPDs are classified within the hematological neoplasms. There are four main myeloproliferative diseases, which can be further categorized by the presence of the Philadelphia chromosome:
 Philadelphia Chromosome "positive"

• Chronic myelogenous leukemia (CML)

 Philadelphia Chromosome "negative"

• Polycythemia vera (PV)
• Essential thrombocytosis (ET)
• Myelofibrosis (MF)
• chronic eosinophilic leukemia / hypereosinophilic syndrome
• chronic neutrophilic leukemia

In 2001, the World Health Organization classified "chronic eosinophilic leukemia / hypereosinophilic syndrome" and "chronic neutrophilic leukemia" under "Chronic myeloproliferative diseases".

Etiology

The myeloproliferative disorders polycythaemia vera (PV), essential thombocythaemia (ET), and primary myelofibrosis (PMF) are clonal disorders of multipotent haematopoietic progenitors.

The genetic cause of these diseases was not known until 2005, when several independent groups demonstrated that most patients with PV, ET and PMF acquire a single point mutation in the cytoplasmic tyrosine kinase JAK2 (JAK2V617F).

See also

 JAKs

References

 Levine RL, Pardanani A, Tefferi A, Gilliland DG. Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nat Rev Cancer. 2007 Sep;7(9):673-83. PMID: 17721432

 Campbell PJ, Green AR. The myeloproliferative disorders. N Engl J Med. 2006 Dec 7;355(23):2452-66. PMID: 17151367

 James C, Ugo V, Casadevall N, Constantinescu SN, Vainchenker W. A JAK2 mutation in myeloproliferative disorders: pathogenesis and therapeutic and scientific prospects. Trends Mol Med. 2005 Nov 2; PMID: 16271512