Myeloproliferative neoplasm overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2] Shyam Patel [3]
Overview
The myeloproliferative neoplasm are a group of diseases of the bone marrow in which excess cells are produced. Myeloproliferative neoplasm may be classified according to the World Health Organization into eight subtypes (chronic myelogenous leukemia, BCR-ABL1–positive, chronic neutrophilic leukemia, polycythemia vera, primary myelofibrosis, essential thrombocythemia, chronic eosinophilic leukemia, not otherwise specified, mastocytosis, myeloproliferative neoplasms, unclassifiable).[1][2] 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. Clinical and pathologic features in the myeloproliferative neoplasms are due to dysregulated proliferation and expansion of myeloid progenitors in the bone marrow, resulting in altered populations of granulocytes, erythrocytes, or platelets in the peripheral blood. Myeloproliferative neoplasm is caused by a mutation in the BCR-ABL, Janus kinase 2, and calreticulin genes.[3][4] Patients may be asymptomatic at diagnosis. However, if symptoms present, symptoms of myeloproliferative neoplasm include fever, fatigue, and bleeding.[5][6] The mainstay of therapy for myeloproliferative neoplasm is chemotherapy, aspirin, and palliative care.[7]
Historical Perspective
The first description of myeloproliferative neoplasm dates back to the late 19th century, when Sir Louis Vasquez studied a patient with excess red blood cells. Myeloproliferative neoplasm was first brought to attention as an important clinical entity by Dr. William Dameshek, an American hematologist, in 1951. In 2005, the link between the JAK2 mutation and polycythemia vera was discovered. The World Health Organization created diagnostic criteria for myeloproliferative neoplasms in 2008, and this was revised in 2016.
Classification
Myeloproliferative neoplasm may be classified according to the World Health Organization into eight subtypes: polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic myelogenous leukemia, chronic neutrophilic leukemia, chronic eosinophilic leukemia, myeloproliferative neoplasms unclassifiable, and mastocytosis. Each subtypes is based on a distinct malignant cell, and each subtype has different criteria for diagnosis.
Pathophysiology
The pathophysiology of myeloproliferative neoplasms is based on the specific subtype of myeloproliferative neoplasm. Each of the 8 different myeloproliferative neoplasms have a slightly different pathophysiologic basis. Primary cytogenetic abnormalities have not been identified in the majority of myeloproliferative neoplasms. Aberrant activation of tyrosine kinases and associated signaling pathways is frequently implicated as the disease-initiating event for many of the myeloproliferative neoplasms. Clinical and pathologic features in the myeloproliferative neoplasms are due to dysregulated proliferation and expansion of myeloid progenitors in the bone marrow, resulting in altered populations of granulocytes, erythrocytes, or platelets in the peripheral blood.
Causes
Myeloproliferative neoplasm is caused by mutations in various genes. Different gene mutations are responsible for each of the 8 subtypes of myeloproliferative neoplasms. [3][4][3] Importantly, multiple different gene mutations can cause a single disease.
Differentiating Myeloproliferative Neoplasm from other Diseases
Myeloproliferative neoplasm must be differentiated from acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, essential thrombocytosis, hypereosinophilic syndrome, non-Hodgkin lymphoma, primary myelofibrosis, secondary thrombocytosis, splenomegaly, systemic mastocytosis, and waldenstrom macroglobulinemia.
Epidemiology and Demographics
The incidence of myeloproliferative neoplasm is approximately 7.8 per 100,000 individuals worldwide.[8]
Risk factors
There are no established risk factors for myeloproliferative neoplasm.
Screening
Screening for myeloproliferative neoplasm by quantitative cell-based JAK2V617F mutation assays may be helpful among patients with erythrocytosis, thrombocytosis, splanchnic vein thrombosis, and unexplained BCR-ABL negative granulocytosis.[9]
Natural History, Complications and Prognosis
If left untreated, patients with myeloproliferative neoplasm may progress to develop weight loss, fever, and night sweats. Common complications of myeloproliferative neoplasm include splenomegaly, bleeding, and thrombosis. Prognosis is generally good with treatment, and the 3-year survival rate of patients with myeloproliferative neoplasm is approximately 35%.[10][5]
Diagnosis
History and Symptoms
Patients may be asymptomatic at diagnosis. However, if symptoms present, symptoms of myeloproliferative neoplasm include fever, fatigue, and bleeding.[5][6]
Physical Examination
Patients with myeloproliferative neoplasm are usually well-appearing. Physical examination of patients with chronic myelogenous leukemia is usually remarkable for skin bruising , fever, splenomegaly, and lymphadenopathy.[5]
Laboratory Findings
Laboratory findings consistent with the diagnosis of myeloproliferative neoplasm include leukocytosis, thrombocytopenia, and anemia.[6][11][12][13]
Chest X-Ray
Chest x-ray may be helpful in the diagnosis of myeloproliferative neoplasm. Findings on chest x-ray suggestive of chronic myelogenous leukemia include enlarged mediastinal lymph nodes, enlarged thymus gland, and pneumonia.[6]
Abdominal CT
Abdominal and chest CT scan may be helpful in the diagnosis of myeloproliferative neoplasm. Findings on CT scan suggestive of myeloproliferative neoplasm include enlarged lymph nodes, splenomegaly, and splanchnic venous thrombosis.[6]
Brain MRI
Brain MRI may be helpful in the detection of brain metastasis in patients with myeloproliferative neoplasm.[6]
Abdominal Ultrasound
Abdominal ultrasound may be helpful in the diagnosis of myeloproliferative neoplasm. Findings on abdominal ultrasound suggestive of myeloproliferative neoplasm include enlarged lymph nodes, splenomegaly, and hypodense liver lesions.[6]
Other Diagnostic Studies
Other diagnostic studies for myeloproliferative neoplasm include bone marrow aspiration and trephine biopsy, lumbar puncture, and lymph node biopsy.[6][14]
Other Imaging Studies
Other imaging studies for myeloproliferative neoplasm include PET scan, which helps to detect metastasis in bone marrow and to follow up medical treatment.[15]
Treatment
Medical Therapy
The mainstay of therapy for myeloproliferative neoplasm is chemotherapy, aspirin, and palliative care.[7]
Surgery
Surgical intervention is recommended for the management of chronic myelogenous leukemia in case of splenectomy.[16]
Primary Prevention
There is no established method for prevention of myeloproliferative neoplasm.[7]
Secondary Prevention
There is no established method for prevention of myeloproliferative neoplasm.[7]
References
- ↑ Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A; et al. (2009). "The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes". Blood. 114 (5): 937–51. doi:10.1182/blood-2009-03-209262. PMID 19357394.
- ↑ Valent P, Horny HP, Escribano L, Longley BJ, Li CY, Schwartz LB; et al. (2001). "Diagnostic criteria and classification of mastocytosis: a consensus proposal". Leuk Res. 25 (7): 603–25. PMID 11377686.
- ↑ 3.0 3.1 3.2 Ganfyd. Polycythaemia vera 2015.http://www.ganfyd.org/index.php?title=Polycythemia_vera
- ↑ 4.0 4.1 Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID http://dx.doi.org/10.1182/blood-2013-11-538983 Check
|pmid=value (help). - ↑ 5.0 5.1 5.2 5.3 Agarwal MB, Malhotra H, Chakrabarti P, Varma N, Mathews V, Bhattacharyya J; et al. (2015). "Myeloproliferative neoplasms working group consensus recommendations for diagnosis and management of primary myelofibrosis, polycythemia vera, and essential thrombocythemia". Indian J Med Paediatr Oncol. 36 (1): 3–16. doi:10.4103/0971-5851.151770. PMC 4363847. PMID 25810569.
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 Canadian Cancer Society.2015.http://www.cancer.ca/en/cancer-information/cancer-type/leukemia-chronic-myelogenous-cml/signs-and-symptoms/?region=ab
- ↑ 7.0 7.1 7.2 7.3 National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/leukemia/hp/cml-treatment-pdq#section/_19
- ↑ Centers for Disease Control and Prevention. WTC Health Program.Myeloid Malignancieshttp://www.cdc.gov/wtc/pdfs/WTCHP_PP_MyeloidMalignancies_02012014.pdf
- ↑ Tefferi A, Noel P, Hanson CA (2011). "Uses and abuses of JAK2 and MPL mutation tests in myeloproliferative neoplasms a paper from the 2010 William Beaumont hospital symposium on molecular pathology". J Mol Diagn. 13 (5): 461–6. doi:10.1016/j.jmoldx.2011.05.007. PMC 3157620. PMID 21723416.
- ↑ Ma X, Does M, Raza A, Mayne ST (2007). "Myelodysplastic syndromes: incidence and survival in the United States". Cancer. 109 (8): 1536–42. doi:10.1002/cncr.22570. PMID 17345612.
- ↑ James W. Vardiman (2009). "Chronic myelogenous leukemia, BCR-ABL1+". American journal of clinical pathology. 132 (2): 250–260. doi:10.1309/AJCPUN89CXERVOVH. PMID 19605820. Unknown parameter
|month=ignored (help) - ↑ Sánchez-Muñoz, Laura; Alvarez-Twose, Ivan; García-Montero, Andrés C; Teodosio, Cristina; Jara-Acevedo, María; Pedreira, Carlos E; Matito, Almudena; Morgado, Jose Mario T; Sánchez, Maria Luz; Mollejo, Manuela; Gonzalez-de-Olano, David; Orfao, Alberto; Escribano, Luis (2011). "Evaluation of the WHO criteria for the classification of patients with mastocytosis". Modern Pathology. 24 (9): 1157–1168. doi:10.1038/modpathol.2011.84. ISSN 0893-3952.
- ↑ Levene, Malcolm I.; Lewis, S. M.; Bain, Barbara J.; Imelda Bates. Dacie & Lewis Practical Haematology. London: W B Saunders. p. 586. ISBN 0-443-06377-X.
- ↑ Levene, Malcolm I.; Lewis, S. M.; Bain, Barbara J.; Imelda Bates. Dacie & Lewis Practical Haematology. London: W B Saunders. p. 586. ISBN 0-443-06377-X.
- ↑ Agool A, Glaudemans AW, Boersma HH, Dierckx RA, Vellenga E, Slart RH (2011). "Radionuclide imaging of bone marrow disorders". Eur J Nucl Med Mol Imaging. 38 (1): 166–78. doi:10.1007/s00259-010-1531-0. PMC 3005118. PMID 20625724.
- ↑ Santos FP, Tam CS, Kantarjian H, Cortes J, Thomas D, Pollock R; et al. (2014). "Splenectomy in patients with myeloproliferative neoplasms: efficacy, complications and impact on survival and transformation". Leuk Lymphoma. 55 (1): 121–7. doi:10.3109/10428194.2013.794269. PMC 3874259. PMID 23573823.