Myeloproliferative disease

Myeloproliferative disease
Classification and external resources
ICD-10	D47.1
ICD-9	205.1, 238.4, 289.89, 289.9
ICD-O:	9950/0-9964/3
MeSH	D009196

The myeloproliferative diseases (MPDs, myeloproliferative neoplasms, MPNs) are a group of diseases of the bone marrow in which excess cells are produced. They 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.^[1] In the most recent World Health Organization classification of Hematologic malignancies, this group of diseases was renamed from "myeloproliferative diseases" to "myeloproliferative neoplasms".^[2] This reflects the underlying clonal genetic changes that are a salient feature of this group of disease.

Classification

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"	Philadelphia Chromosome "negative"
Chronic myelogenous leukemia (CML)	Polycythemia vera (PV) Essential thrombocytosis (ET) Myelofibrosis (MF)

In 2001, the World Health Organization classified "chronic eosinophilic leukemia / hypereosinophilic syndrome" and chronic neutrophilic leukemia under "Chronic myeloproliferative diseases".^[3]

Causes

All MPDs arise from precursors of the myeloid lineage in the bone marrow. The lymphoid lineage may produce similar diseases, the lymphoproliferative disorders (acute lymphoblastic leukemia, lymphomas, chronic lymphocytic leukemia and multiple myeloma).

Diagnosis

Depending on the nature of the myeloproliferative disorder, diagnostic tests may include red cell mass determination (for polycythemia), bone marrow aspirate and trephine biopsy, arterial oxygen saturation and carboxyhaemoglobin level, neutrophil alkaline phosphatase level, vitamin B₁₂ (or B₁₂ binding capacity) and serum urate.^[4]

According to the WHO Classification of Hematopoietic and Lymphoid Neoplasms 2008 myeloproliferative disorders are divided into the following by diagnostic characteristics:

1. Chronic myelogenous leukemia (CML)

with defining translocation t(9;22) BCR-ABL translocation which has three breakpoints:
a. u-BCR-ABL (p230): leads to CML with usual neutrophilia and basophilia
b. minor-BCR-ABL (p190): leads to CML which has a tendency to become acute lymphoblastic leukemia (ALL) usually precursor B ALL and rarely precursor T ALL
c. major-BCR-ABL (p210): normal usual breakpoint

2. Primary myelofibrosis

associated with JAK2 mutation in up to 50% of cases and MPL (thrombopoietin receptor) mutation in up to 5% of cases:
a. Cellular phase - increased megakaryocytes which cluster, reticulin fibrosis, later trichrome (collagenous) fibrosis, and increased myeloid precursors
b. Fibrotic phase - collagenous fibrosis with lack of marrow elements

3. Polycythemia vera

associated most often with JAK2 mutation in up to 80% of cases:
a. Cellular phase - increased megakaryocytes which cluster, reticulin fibrosis, later trichrome fibrosis, and increased myeloid and erythroid precursors
b. Fibrotic phase - collagenous fibrosis with lack of marrow elements

4. Essential Thrombocythemia

associated with JAK2 mutation in up to 20% of cases and MPL (thrombopoietin receptor) mutation in up to 15% of cases:
a. Cellular phase - increased large megakaryocytes with fibrosis and little increase in other bone marrow elements
b. Fibrotic phase - collagenous fibrosis with lack of marrow elements

These disorders are still being revised according to more specific genetic mutations and how often patients end in a fibrotic marrow event.

In 2005, the discovery of the JAK2 V617F mutation provided some evidence to suggest a common pathogenesis for the Philadelphia Chromosome negative MPDs.^{[5][6][7][8][9]}

Treatment

While investigational drug therapies exist, there is currently not a curative drug treatment for MPDs. The goal of treatment for ET and PV is to prevent thromohemorragic complications. The goal of treatment for MF is to alleviate anemia, splenomegaly, and other symptoms. Low-dose aspirin is effective in PV and ET. Tyrosine kinase inhibitors have improved the prognosis of CML patients.^[2]

References

1. ^ Dameshek W (1951). "Some speculations on the myeloproliferative syndromes". Blood 6 (4): 372–5. PMID 14820991. 
2. ^ ^{a b} Tefferi A, Vainchenker W (February 2011). "Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies". J. Clin. Oncol. 29 (5): 573–82. doi:10.1200/JCO.2010.29.8711. PMID 21220604. 2
3. ^ "Classification of Human Hematopoietic Malignancies". http://emice.nci.nih.gov/emice/mouse_models/organ_models/hema_models/hema_human_class. 
4. ^ Levene, Malcolm I.; Lewis, S. M.; Bain, Barbara J.; Imelda Bates (2001). Dacie & Lewis Practical Haematology. London: W B Saunders. p. 586. ISBN 0-443-06377-X. 
5. ^ Baxter EJ, Scott LM, Campbell PJ, et al. (2005). "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders". Lancet 365 (9464): 1054–1061. doi:10.1016/S0140-6736(05)71142-9. PMID 15781101. 
6. ^ James C, Ugo V, Le Couedic JP, et al. (2005). "A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera". Nature 434 (7037): 1144–1148. doi:10.1038/nature03546. PMID 15793561. 
7. ^ Levine RL, Wadleigh M, Cools J, et al. (2005). "Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis". Cancer Cell 7 (4): 387–397. doi:10.1016/j.ccr.2005.03.023. PMID 15837627. 
8. ^ Kralovics R, Passamonti F, Buser AS, et al. (2005). "A gain-of-function mutation of JAK2 in myeloproliferative disorders". N Engl J Med 352 (17): 1779–1790. doi:10.1056/NEJMoa051113. PMID 15858187. 
9. ^ Campbell PJ, Scott LM, Buck G, et al. (2005). "Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study". Lancet 366 (9501): 1945–1953. doi:10.1016/S0140-6736(05)67785-9. PMID 16325696. 

External links

• MeSH Myeloproliferative+Disorders
• Myeloproliferative Disorders Website of The CMPD Education Foundation
• Myeloproliferative Disorders in practice
• Myeloproliferative Disorders Research Consortium