eMedicine Specialties > Hematology > Stem Cells and Disorders
Myeloproliferative Disease
Updated: Feb 13, 2008
Introduction
Background
Myeloproliferative diseases (MPDs) are a heterogenous group of disorders characterized by cellular proliferation of one or more hematologic cell lines in the peripheral blood, distinct from acute leukemia.
According to the French-American-British (FAB) classification, chronic myeloproliferative diseases consist of 4 diseases: chronic myelogenous leukemia (CML); polycythemia vera (PV); essential thrombocythemia (ET); and agnogenic myeloid metaplasia (AMM), which is also known as myelofibrosis (MF). In 2002, the World Health Organization (WHO) proposed an alternate classification schema for these diseases, adding chronic neutrophilic leukemia (CNL) and chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome (HES).1 For a comparison of these classification systems, see the table below.
A related disorder, systemic mastocytosis (SM), has many features in common with the myeloproliferative diseases and is considered by some authors to belong to this group. In some patients, conditions overlap, and clear categorization may be difficult. Myeloproliferative disease may evolve into one of the other myeloproliferative conditions, transform to acute leukemia, or both.
Comparison of FAB and WHO Classifications of Chronic Myeloproliferative Diseases.
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Table
| FAB | WHO |
| Chronic myelogenous leukemia | Chronic myelogenous leukemia |
| Polycythemia vera | Polycythemia vera |
| Essential thrombocythemia | Essential thrombocythemia |
| Agnogenic myeloid metaplasia/myelofibrosis | Chronic idiopathic myelofibrosis |
| ... | Chronic neutrophilic leukemia |
| ... | Chronic eosinophilic leukemia/hypereosinophilic syndrome |
| FAB | WHO |
| Chronic myelogenous leukemia | Chronic myelogenous leukemia |
| Polycythemia vera | Polycythemia vera |
| Essential thrombocythemia | Essential thrombocythemia |
| Agnogenic myeloid metaplasia/myelofibrosis | Chronic idiopathic myelofibrosis |
| ... | Chronic neutrophilic leukemia |
| ... | Chronic eosinophilic leukemia/hypereosinophilic syndrome |
Some evidence indicates that myeloproliferative diseases arise from malignant transformation of a single stem cell. Involvement of erythropoiesis, neutrophilopoiesis, eosinophilopoiesis, basophilopoiesis, monocytopoiesis, and thrombopoiesis occurs in the chronic phase of chronic myelogenous leukemia. Some evidence also indicates that lymphocytes are derived from primordial malignant cells. This is based on observations that a single isoenzyme for glucose-6-phosphate dehydrogenase (G-6-PD) is present in some T and B lymphocytes in women with chronic myelogenous leukemia who are heterozygous for isoenzymes A and B.
See CME available on Chronic Myeloproliferative Disorders and Advances in the Treatment of Chronic Myeloid Leukemia.
Pathophysiology
Data from G-6-PD studies, cytogenetic analyses, and molecular methods have established the clonal origin of myeloproliferative diseases; this clonality potentially occurs at different stem cell levels. An attribute common to these disorders appears to be an acquired activating mutation in the gene coding for various tyrosine kinases.
In chronic myelogenous leukemia, the tyrosine kinase activity of the bcr-abl hybrid gene is increased. In polycythemia vera, essential thrombocythemia, and myelofibrosis, the prevalent genetic lesion appears to be a valine to phenylalanine substitution at amino acid position 617 (V617F) within the Janus kinase 2 (JAK2) gene.2,3 This produces hypersensitivity to erythropoietin. At least in myelofibrosis patients the leukemic transformation is probably not related to JAK-2 (V617F) mutation status.4 Systemic mastocytosis has been linked with the D816 mutation of the KIT gene. The FIP1L1-PDGFR mutation has been identified in a subgroup of people with systemic mastocytosis with eosinophilia (SM-eos).
Frequency
United States
Approximately 4300 new cases of chronic myelogenous leukemia are diagnosed in the United States every year, accounting for more than half of myeloproliferative disease cases. The incidence of polycythemia vera in the United States is approximately 5-17 cases per 1 million population per year. True incidences of essential thrombocythemia and myelofibrosis are not known because epidemiological studies on these disorders are inadequate.
International
The incidence of polycythemia vera is 0.02-2.8 per 100,000 per year; Japan has the lowest incidence. Essential thrombocythemia has an incidence of 0.1-1.5 per 100,000 per year. Myelofibrosis has an international incidence of 0.4-0.9 per 100,000 per year.
Mortality/Morbidity
In the United States, 2,400 deaths every year are secondary to chronic myelogenous leukemia. Exact mortality and morbidity rates of other myeloproliferative diseases are unknown.
Race
Chronic myelogenous leukemia appears to affect all races with approximately equal frequency. The incidences of polycythemia vera, essential thrombocythemia, and myelofibrosis were tenfold higher among Ashkenazi Jews in northern Israel than in persons of Arabic descent in the region.
Sex
The female-to-male ratio is 1:1.4.
Age
Most cases encountered in clinical practice are in patients aged 40-60 years. Myeloproliferative diseases are uncommon in people younger than 20 years and are rare in childhood.
Clinical
History
- Easy fatigability
- Anorexia, weight loss
- Abdominal discomfort and early satiety secondary to splenomegaly is more common in chronic myelogenous leukemia and agnogenic myeloid metaplasia.
- Easy bruising, bleeding, and/or symptoms of thrombosis
- Swollen, painful joint(s) secondary to gouty arthritis secondary to hyperuricemia
- Priapism, tinnitus, or stupor from leukostasis
- Left upper quadrant and left shoulder pain as a consequence of splenic infarction and perisplenitis
- In many patients, abnormal blood counts are noted on a blood test performed for other reasons.
Physical
- Pallor, except in patients with polycythemia vera
- Plethora secondary to polycythemia
- Petechiae and/or ecchymosis
- Palpable spleen and/or liver
- Occasionally, syndrome of fever accompanied by painful maculopapular violaceous lesions on trunk, arms, legs, and face, which is called acute febrile neutrophilic dermatosis or Sweet syndrome
Causes
As with other malignant disorders, the precise cause of myeloproliferative disease is unknown. The etiology is complex, incompletely understood, and likely a multistep process involving more than one gene.
Philadelphia chromosome, t(9:22), is found in most patients who have chronic myelogenous leukemia. Even when the Philadelphia chromosome is negative, the gene bcr-abl, formed as result of t(9:22), tests positive in patients with chronic myelogenous leukemia using molecular techniques. Bcr-abl encodes a fusion protein with tyrosine kinase activity, which is constitutively expressed and is regarded as the central mechanism that underlies the chronic phase of chronic myelogenous leukemia.5More on Myeloproliferative Disease |
 Overview: Myeloproliferative Disease |
| Differential Diagnoses & Workup: Myeloproliferative Disease |
| Treatment & Medication: Myeloproliferative Disease |
| Follow-up: Myeloproliferative Disease |
| Multimedia: Myeloproliferative Disease |
| References |
| Next Page » |
References
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Levine RL, Wadleigh M, Cools J. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. Apr 2005;7(4):387-97. [Medline].
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Pardanani A, Brockman SR, Paternoster SF. FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia. Blood. Nov 15 2004;104(10):3038-45. [Medline]. [Full Text].
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Further Reading
Keywords
MPD, polycythemia vera, PV, polycythemia rubra vera, primary thrombocythemia, PT, agnogenic myeloid metaplasia, AMM, chronic myelogenous leukemia, chronic myeloid leukemia, CML, myelofibrosis, MF, acute leukemia, myelodysplastic syndrome, essential thrombocythemia, ET, Budd-Chiari syndrome, chronic idiopathic myelofibrosis, CIM, chronic neutrophilic leukemia, CNL, chronic eosinophilic leukemia, CEL, hypereosinophilic syndrome, HES
