View source for Myeloproliferative neoplasm overview

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{{Myeloproliferative disease}}
{{CMG}}{{AE}}{{MJK}} {{shyam}}
==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).<ref name="pmid19357394">{{cite journal| author=Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al.| title=The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. | journal=Blood | year= 2009 | volume= 114 | issue= 5 | pages= 937-51 | pmid=19357394 | doi=10.1182/blood-2009-03-209262 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19357394  }} </ref><ref name="pmid11377686">{{cite journal| author=Valent P, Horny HP, Escribano L, Longley BJ, Li CY, Schwartz LB et al.| title=Diagnostic criteria and classification of mastocytosis: a consensus proposal. | journal=Leuk Res | year= 2001 | volume= 25 | issue= 7 | pages= 603-25 | pmid=11377686 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11377686  }} </ref> 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.<ref name="ganfyd">Ganfyd. Polycythaemia vera 2015.http://www.ganfyd.org/index.php?title=Polycythemia_vera</ref><ref name="pmidhttp://dx.doi.org/10.1182/blood-2013-11-538983">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid=http://dx.doi.org/10.1182/blood-2013-11-538983 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10  }} </ref> Patients may be [[asymptomatic]] at diagnosis. However, if symptoms present, symptoms of myeloproliferative neoplasm include [[fever]], [[fatigue]], and [[bleeding]].<ref name="pmid25810569">{{cite journal| author=Agarwal MB, Malhotra H, Chakrabarti P, Varma N, Mathews V, Bhattacharyya J et al.| title=Myeloproliferative neoplasms working group consensus recommendations for diagnosis and management of primary myelofibrosis, polycythemia vera, and essential thrombocythemia. | journal=Indian J Med Paediatr Oncol | year= 2015 | volume= 36 | issue= 1 | pages= 3-16 | pmid=25810569 | doi=10.4103/0971-5851.151770 | pmc=PMC4363847 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25810569  }} </ref><ref name="cancer.ca">Canadian Cancer Society.2015.http://www.cancer.ca/en/cancer-information/cancer-type/leukemia-chronic-myelogenous-cml/signs-and-symptoms/?region=ab</ref> The mainstay of therapy for myeloproliferative neoplasm is [[chemotherapy]], [[aspirin]], and palliative care.<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/leukemia/hp/cml-treatment-pdq#section/_19</ref>

==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 kinase]]s 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. Importantly, multiple different gene mutations can cause a single disease.

==Differentiating Myeloproliferative Neoplasm from other Diseases==
Myeloproliferative neoplasm must be differentiated from [[myelodysplastic syndrome]], [[acute myelogenous leukemia]], [[acute lymphoblastic leukemia, [[Waldenstrom's macroglobulinemia]], and [[lymphoproliferative disorder]]. Each of these conditions has unique set of causes, laboratory abnormalities, physical exam findings, and therapies.

==Epidemiology and Demographics==
The incidence of myeloproliferative neoplasm is approximately 7.8 per 100,000 individuals worldwide. The different subtypes of myeloproliferative neoplasm have different incidence and prevalence statistics. Males are more commonly affected than females, and older persons are more commonly affected than younger persons.

==Risk factors==
There are four major categories of risk factors for myeloproliferative neoplasm. Genetic mutational events comprise the most common risk factor. Other risk factors include advanced age, prior cytotoxic chemotherapy, and autoimmune disease.

==Screening==
There are currently no guidelines for screening for myeloproliferative neoplasm. Monitoring of the complete blood count is done routinely.

==Natural History, Complications and Prognosis==
The natural history of myeloproliferative neoplasm begins with weight loss, fever, and night sweats. The natural history depends on the subtype of myeloproliferative neoplasm. Common complications of myeloproliferative neoplasm include [[splenomegaly]], bleeding, [[thrombosis]], bone marrow fibrosis, and acute leukemia. Prognosis depends on the subtype of myeloproliferative neoplasm. Each subtype has its own prognostic scoring system. In general, patients with [[polycythemia vera]], [[essential thrombocythemia]], and [[chronic myeloid leukemia]] have better prognosis than patients with [[primary myelofibrosis]]. The prognosis is generally good with treatment.

==Diagnosis==
===History and Symptoms===
Patients may be [[asymptomatic]] at diagnosis. However, if symptoms present, symptoms of myeloproliferative neoplasm include [[fever]], [[fatigue]], and [[bleeding]].

===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]].

===Laboratory Findings===
Laboratory findings consistent with the diagnosis of myeloproliferative neoplasm include [[leukocytosis]], [[thrombocytopenia]], and [[anemia]].<ref name="cancer.ca">Canadian Cancer Society.2015.http://www.cancer.ca/en/cancer-information/cancer-type/leukemia-chronic-myelogenous-cml/diagnosis/?region=ab</ref><ref>{{Cite journal
 | author = [[James W. Vardiman]]
 | title = Chronic myelogenous leukemia, BCR-ABL1+
 | journal = [[American journal of clinical pathology]]
 | volume = 132
 | issue = 2
 | pages = 250–260
 | year = 2009
 | month = August
 | doi = 10.1309/AJCPUN89CXERVOVH
 | pmid = 19605820
}}</ref><ref name="Sánchez-MuñozAlvarez-Twose2011">{{cite journal|last1=Sánchez-Muñoz|first1=Laura|last2=Alvarez-Twose|first2=Ivan|last3=García-Montero|first3=Andrés C|last4=Teodosio|first4=Cristina|last5=Jara-Acevedo|first5=María|last6=Pedreira|first6=Carlos E|last7=Matito|first7=Almudena|last8=Morgado|first8=Jose Mario T|last9=Sánchez|first9=Maria Luz|last10=Mollejo|first10=Manuela|last11=Gonzalez-de-Olano|first11=David|last12=Orfao|first12=Alberto|last13=Escribano|first13=Luis|title=Evaluation of the WHO criteria for the classification of patients with mastocytosis|journal=Modern Pathology|volume=24|issue=9|year=2011|pages=1157–1168|issn=0893-3952|doi=10.1038/modpathol.2011.84}}</ref><ref>{{cite book |author=Levene, Malcolm I.; Lewis, S. M.; Bain, Barbara J.; Imelda Bates|title=Dacie & Lewis Practical Haematology |publisher=W B Saunders |location=London |year= |pages= |isbn=0-443-06377-X |pages=586}}</ref>
===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]].<ref name="cancer.ca">Canadian Cancer Society.2015.http://www.cancer.ca/en/cancer-information/cancer-type/leukemia-chronic-myelogenous-cml/diagnosis/?region=ab</ref>
===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.<ref name="cancer.ca">Canadian Cancer Society.2015.http://www.cancer.ca/en/cancer-information/cancer-type/leukemia-chronic-myelogenous-cml/diagnosis/?region=ab</ref>
===Brain MRI===
Brain MRI may be helpful in the detection of brain metastasis in patients with myeloproliferative neoplasm.<ref name="cancer.ca">Canadian Cancer Society.2015.http://www.cancer.ca/en/cancer-information/cancer-type/leukemia-chronic-myelogenous-cml/diagnosis/?region=ab</ref>
===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.<ref name="cancer.ca">Canadian Cancer Society.2015.http://www.cancer.ca/en/cancer-information/cancer-type/leukemia-chronic-myelogenous-cml/diagnosis/?region=ab</ref>
===Other Diagnostic Studies===
Other diagnostic studies for myeloproliferative neoplasm include [[bone marrow aspiration]] and [[biopsy|trephine biopsy]], [[lumbar puncture]], and [[lymph node biopsy]].<ref name="cancer.ca">Canadian Cancer Society.2015.http://www.cancer.ca/en/cancer-information/cancer-type/leukemia-chronic-myelogenous-cml/diagnosis/?region=ab</ref><ref>{{cite book |author=Levene, Malcolm I.; Lewis, S. M.; Bain, Barbara J.; Imelda Bates|title=Dacie & Lewis Practical Haematology |publisher=W B Saunders |location=London |year= |pages= |isbn=0-443-06377-X |pages=586}}</ref>
===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.<ref name="pmid20625724">{{cite journal| author=Agool A, Glaudemans AW, Boersma HH, Dierckx RA, Vellenga E, Slart RH| title=Radionuclide imaging of bone marrow disorders. | journal=Eur J Nucl Med Mol Imaging | year= 2011 | volume= 38 | issue= 1 | pages= 166-78 | pmid=20625724 | doi=10.1007/s00259-010-1531-0 | pmc=PMC3005118 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20625724  }} </ref>

==Treatment==
===Medical Therapy===
The mainstay of therapy for myeloproliferative neoplasm is [[chemotherapy]], [[aspirin]], and palliative care.<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/leukemia/hp/cml-treatment-pdq#section/_19</ref>
===Surgery===
Surgical intervention is recommended for the management of chronic myelogenous leukemia in case of [[splenectomy]].<ref name="pmid23573823">{{cite journal| author=Santos FP, Tam CS, Kantarjian H, Cortes J, Thomas D, Pollock R et al.| title=Splenectomy in patients with myeloproliferative neoplasms: efficacy, complications and impact on survival and transformation. | journal=Leuk Lymphoma | year= 2014 | volume= 55 | issue= 1 | pages= 121-7 | pmid=23573823 | doi=10.3109/10428194.2013.794269 | pmc=PMC3874259 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23573823  }} </ref>
===Primary Prevention===
There is no established method for prevention of myeloproliferative neoplasm.<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/myeloproliferative</ref>
===Secondary Prevention===
There is no established method for prevention of myeloproliferative neoplasm.<ref name="cancergov">National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/myeloproliferative</ref>

==References==
{{Reflist|2}}
[[Category:Hematology]] 

[[Category: Disease]]

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