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bring disorder to (同)disarray
a physical condition in which there is a disturbance of normal functioning; "the doctor prescribed some medicine for the disorder"; "everyone gets stomach upsets from time to time" (同)upset
a disturbance of the peace or of public order
not arranged in order (同)unordered

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〈U〉『無秩序』,混乱,乱雑(confusion) / 《しばしば複数形で》(社会的・政治的な)粉争,騒動 / 〈C〉(肉体的・精神的な)不調,異常,障害 / …‘の'秩序を乱す / 〈心身〉‘に'異常を起こさせる

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/08/16 17:19:07」(JST)

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The myeloproliferative diseases (MPDs) or 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[edit source | edit]

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[edit source | edit]

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).

Most cases have an activating JAK2 or MPL mutation.^[4] A smaller subset also have mutations in the genes LNK, CBL, TET2, ASXL1, IDH, IKZF1 or EZH2. The pathogenetic contribution of these mutations is being studied. 96% of patients with polycythemia vera have a V617F mutation in exon 14 of JAK2.^[5]

Diagnosis[edit source | edit]

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.^[6]

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)[edit source | edit]

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 (PMF)[edit source | edit]

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 (PV)[edit source | edit]

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 (ET)[edit source | edit]

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.^[7]^[8]^[9]^[10]^[11]

Treatment[edit source | edit]

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 thrombohemorragic 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.^[4]

Recently a JAK2 inhibitor has been approved for use in primary myelofibrosis.^[12] Trials of these inhibitors are in progress for the treatment of the other myeloproliferative disorders.

References[edit source | edit]

^ Dameshek W (1951). "Some speculations on the myeloproliferative syndromes". Blood 6 (4): 372–5. PMID 14820991.
^ 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
^ "Classification of Human Hematopoietic Malignancies".
^ ^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.
^ Passamonti F, Maffioli M, Caramazza D, Cazzola M (June 2011). "Myeloproliferative neoplasms: from JAK2 mutations discovery to JAK2 inhibitor therapies". Oncotarget 2 (6): 485–90. PMC 3248205. PMID 21646683.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ Tibes R, Bogenberger JM, Benson KL, Mesa RA (October 2012). "Current outlook on molecular pathogenesis and treatment of myeloproliferative neoplasms". Mol Diagn Ther 16 (5): 269–83. doi:10.1007/s40291-012-0006-3. PMID 23023734.

External links[edit source | edit]

Myeloproliferative Disorders at the US National Library of Medicine Medical Subject Headings (MeSH)
Myeloproliferative Disorders Website of The CMPD Education Foundation
Myeloproliferative Disorders in practice
Myeloproliferative Disorders Research Consortium
MPN Info via Cancer.gov
Spotlight on MPN

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 骨髄増殖性腫瘍の概要 overview of the myeloproliferative neoplasms
2. 原発性骨髄線維症の臨床症状および診断 clinical manifestations and diagnosis of primary myelofibrosis
3. 骨髄異形成症候群の臨床症状および診断 clinical manifestations and diagnosis of the myelodysplastic syndromes
4. 成人における門脈血栓症の疫学および病因 epidemiology and pathogenesis of portal vein thrombosis in adults
5. 本態性血小板血症の診断および臨床症状 diagnosis and clinical manifestations of essential thrombocythemia

English Journal

Budd-Chiari syndrome in very young adult patients with polycythemia vera: report of case series with good outcome with direct thrombin inhibitor treatment.

Goldstein G, Maor J, Kleinbaum Y, Palumbo M, Sidi Y, Salomon O.SourceaPediatric Hemato-Oncology and Bone Marrow Transplantation, The Edmond and Lily Safra Children Hospital bDepartment of Gastroenterology cDepartment of Diagnostic Imaging dDepartment of Internal Medicine C eThe Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel-Hashomer and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.Blood Coagul Fibrinolysis.2013 Dec;24(8):848-53. doi: 10.1097/MBC.0b013e328364b9e6.
Polycythemia vera is a Philadelphia chromosome-negative myeloproliferative disorder with incidence of 1% under the age of 25. The Budd-Chiari syndrome (BCS) is a well known complication of polycythemia vera even in children, and characterized by occlusion of hepatic outflow. A computerized archive s
PMID 23941968

World health organization group 5 pulmonary hypertension.

Lahm T, Chakinala MM.SourceDivision of Pulmonary, Allergy, Critical Care, Occupational and Sleep Medicine, Department of Medicine, Richard L. Roudebush VA Medical Center, Center for Immunobiology, Indiana University School of Medicine, 980 West Walnut Street, Room C400, Indianapolis, IN 46202, USA. Electronic address: tlahm@iu.edu.
Clinics in chest medicine.Clin Chest Med.2013 Dec;34(4):753-78. doi: 10.1016/j.ccm.2013.08.005. Epub 2013 Oct 18.
World Health Organization (WHO) group 5 pulmonary hypertension (PH) entails a heterogeneous group of disorders that may cause PH by unclear and/or multiple mechanisms. In particular, group 5 includes PH caused by hematologic disorders, systemic diseases, metabolic disorders, chronic renal failure, a
PMID 24267303

Pulmonary hypertension associated with chronic hemolytic anemia and other blood disorders.

Machado RF, Farber HW.SourceSection of Pulmonary, Critical Care Medicine, Sleep and Allergy, Department of Medicine, Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, 909 South Wolcott Avenue, M/C 719, Chicago, IL 60612, USA. Electronic address: machador@uic.edu.
Clinics in chest medicine.Clin Chest Med.2013 Dec;34(4):739-52. doi: 10.1016/j.ccm.2013.08.006. Epub 2013 Oct 17.
Pulmonary hypertension (PH) has emerged as a major complication of several hematologic disorders, including hemoglobinopathies, red cell membrane disorders, chronic myeloproliferative disorders, and splenectomy. With the exception of sickle cell disease, there are a limited number of studies systema
PMID 24267302

Japanese Journal

血小板2次凝集欠如および von Willebrand 病 type 2A を伴った本態性血小板血症の1男児例

庄司朋子,長江千愛,山下敦己,武藤真二,浅原美恵子,木下明俊,瀧正志
日本小児血液学会雑誌 25(2), 102-106, 2011-04-30
NAID 10029312197

骨髄増殖性腫瘍におけるIDH変異の意義

鈴木達也,富田章裕
血液内科 62(4), 492-498, 2011-04
NAID 40019064455

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★リンクテーブル★

リンク元	「好中球アルカリホスファターゼスコア」「骨髄増殖性疾患」
拡張検索	「myeloproliferative disorders」「chronic myeloproliferative disorders」
関連記事	「disorder」