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==Overview==
==Overview==
Myelofibrosis is a hematological disorder in which the bone marrow is replaced with [[collagen|collagenous connective tissue]] and progressive [[fibrosis]], replacing the bone marrow with a scar tissue and hence disrupting the normal production of blood cells which leads to pancytopenia.<ref name="pmid27539616">{{cite journal |vauthors=Shantzer L, Berger K, Pu JJ |title=Primary myelofibrosis and its targeted therapy |journal=Ann. Hematol. |volume=96 |issue=4 |pages=531–535 |date=April 2017 |pmid=27539616 |doi=10.1007/s00277-016-2785-9 |url=}}</ref> It is also classified as a myeloproliferative disorder.<ref name="overviewofmyelofibrosis1">Myelofibrosis. Dr Henry Knipe ◉ and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/myelofibrosis. Accessed on March 7, 2016</ref> The term myelofibrosis alone usually refers to '''primary myelofibrosis (PMF)''', also known as chronic idiopathic myelofibrosis (CIMF); the terms idiopathic and primary mean that the disease is of unknown or spontaneous origin. This is in contrast with myelofibrosis that develops secondary to [[polycythemia vera]], [[essential thrombocythaemia]], [[leukemia]], or [[lymphoma]] ('''secondary myelofibrosis'''). Myelofibrosis is a form of myeloid metaplasia, which refers to a change in cell type in the blood-forming tissue of the bone marrow, and often the two terms are used synonymously.<ref name="myelofibrosisoverviewwiki1">Myelofibrosis. Wikipedia 2016. https://en.wikipedia.org/wiki/Myelofibrosis. Accessed on March 7, 2016</ref> Genes involved in the pathogenesis of myelofibrosis include ''[[JAK2]]'', ''[[Calreticulin|CALR]]'', and ''[[Myeloproliferative leukemia virus oncogene|MPL]]''.<ref name="TefferiLasho2014">{{cite journal|last1=Tefferi|first1=A|last2=Lasho|first2=T L|last3=Finke|first3=C M|last4=Knudson|first4=R A|last5=Ketterling|first5=R|last6=Hanson|first6=C H|last7=Maffioli|first7=M|last8=Caramazza|first8=D|last9=Passamonti|first9=F|last10=Pardanani|first10=A|title=CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons|journal=Leukemia|volume=28|issue=7|year=2014|pages=1472–1477|issn=0887-6924|doi=10.1038/leu.2014.3}}</ref> Myelofibrosis must be differentiated from other diseases that cause diffuse bone sclerosis, such as [[sickle cell disease]], [[hyperthyroidism]], [[dysplasia|sclerosing bone dysplasia]], [[bone metastasis|osteoblastic metastases]], and [[Paget's disease]].<ref name="myelofibrosisdiffdiagnsosiseradio1">Differential diagnosis of myelofibrosis. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/myelofibrosis. Accessed on March 10, 2016</ref><ref name="Diffusebonysclerosisdifferentialdiagnosis1">Diffuse bony sclerosis: differential diagnosis. Dr Craig Hacking and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/diffuse-bony-sclerosis-differential-diagnosis. Accessed on March 10, 2016</ref> Myelofibrosis must be differentiated from other diseases that cause [[splenomegaly]], such as [[anemia]], [[CML]], [[polycythemia rubra vera]], [[cirrhosis]], [[infections]], [[neoplastic]], and [[lipid storage disorder|lipid storage disorders]].<ref name="myelofibrosisdiffdiagnsosiseradio1">Differential diagnosis of myelofibrosis. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/myelofibrosis. Accessed on March 10, 2016</ref><ref name="splenomegalydiffdiagnosisradio1">Splenomegaly. Dr Henry Knipe and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/''Italic text''articles/splenomegaly. Accessed on March 11, 2016</ref> The prevalence of myelofibrosis is approximately 1 per 100,000 individuals worldwide. Myelofibrosis is a disease that tends to affect the middle-aged and elderly population. The mean age at diagnosis is 60 years.<ref name="epidemiologyofmyelofibrosis1radio1">Epidemiology of myelofibrosis. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/myelofibrosis. Accessed on March 8, 2016</ref> Males are more commonly affected with myelofibrosis than females. The male to female ratio is approximately 1.5 to 1.<ref name="pmid22212965">{{cite journal| author=Tefferi A, Lasho TL, Jimma T, Finke CM, Gangat N, Vaidya R et al.| title=One thousand patients with primary myelofibrosis: the mayo clinic experience. | journal=Mayo Clin Proc | year= 2012 | volume= 87 | issue= 1 | pages= 25-33 | pmid=22212965 | doi=10.1016/j.mayocp.2011.11.001 | pmc=PMC3538387 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22212965 }} </ref> Myelofibrosis usually affects individuals of the Ashkenazi Jews race. African American, Latin American, and Asian individuals are less likely to develop myelofibrosis.<ref name="racemf1">Causes. The physician's guide to myelofibrosis 2016. http://nordphysicianguides.org/wp-content/uploads/2012/11/NORD_Physician_Guide_to_Myelofibrosis.pdf. Accessed on March 14, 2016</ref> Common risk factors in the development of myelofibrosis may be age, [[myeloproliferative disorder|other myeloproliferative disorders]], [[radiation]], or industrial chemical exposure.<ref name="riskfactorsofmyelofibrosismayoclinic1">Risk factors for myelofibrosis. Mayo clinic 2016. http://www.mayoclinic.org/diseases-conditions/myelofibrosis/basics/risk-factors/con-20027210. Accessed on March 7, 2016</ref> Myelofibrosis has a very indolent course.<ref name="wikidiagn1osismf1">Diagnosis of myelofibrosis. Wikipedia 2016. https://en.wikipedia.org/wiki/Myelofibrosis. Accessed on March 8, 2016</ref> If left untreated, myelofibrosis may progress to develop [[acute myelogenous leukemia]], [[Blood clots|thrombohemorrhagic events]], and [[Bone marrow failure|progressive marrow failure]]. Common complications of myelofibrosis include [[infections]], [[bleeding]], [[hepatic failure]], [[heart failure]], and [[gout]].<ref name="complicatnmf1">Complications of myelofibrosis. US National Library of Medicine 2016. https://www.nlm.nih.gov/medlineplus/ency/article/000531.htm. Accessed on March 7, 2016</ref><ref name="signsandsymptomsofmyelofibrosiswiki1">Signs and symptoms of myelofibrosis. Wikipedia 2016. https://en.wikipedia.org/wiki/Myelofibrosis. Accessed on March 7, 2016</ref><ref name="KelleYıldız2015">{{cite journal|last1=Kelle|first1=Bayram|last2=Yıldız|first2=Fatih|last3=Paydas|first3=Semra|last4=Bagır|first4=Emine Kılıc|last5=Ergin|first5=Melek|last6=Kozanoglu|first6=Erkan|title=Coexistence of hypertrophic osteoarthropathy and myelofibrosis|journal=Revista Brasileira de Reumatologia (English Edition)|year=2015|issn=22555021|doi=10.1016/j.rbre.2014.11.004}}</ref><ref name="diseaseoverviewmf1">Disease overview of primary myelofibrosis. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_9. Accessed on March 10, 2016</ref><ref name="complmf1radio1">Complications of primary myelofibrosis. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/myelofibrosis. Accessed on March 10, 2016</ref> Prognosis is generally poor and the median survival for myelofibrosis is 3.5 years to 5.5 years, but patients younger than 55 years have a median survival of 11 years.<ref name="diseaseoverviewmf1">Disease overview of primary myelofibrosis. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_9. Accessed on March 10, 2016</ref> According to the World Health Organization (WHO) diagnostic criteria for primary myelofibrosis, [[polycythemia vera]], and [[essential thrombocythemia]], the diagnosis of primary myelofibrosis is made when all three of the following major diagnostic criteria and at least two minor criteria are met.<ref name="diagnosticcriteriamyelofibrosis1">World Health Organization (WHO) Diagnostic Criteria for Primary Myelofibrosis (PMF), Polycythemia Vera (PV), and Essential Thrombocythemia (ET). MPN Connect 2016. http://www.mpnconnect.com/pdf/who-diagnostic-criteria-myelofibrosis.pdf. Accessed on March 8, 2016</ref><ref name="pmid17488875">{{cite journal| author=Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA et al.| title=Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. | journal=Blood | year= 2007 | volume= 110 | issue= 4 | pages= 1092-7 | pmid=17488875 | doi=10.1182/blood-2007-04-083501 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17488875  }} </ref> Symptoms of myelofibrosis include [[abdominal pain|left upper quadrant abdominal pain]], [[bruising]], [[bleeding|easy bleeding]], [[Anemia|pale skin]], and [[infection|frequent infections]].<ref name="symptomsofmyelofibrosis1">Symptoms of myelofibrosis. US National Library of Medicine 2016. https://www.nlm.nih.gov/medlineplus/ency/article/000531.htm. Accessed on March 7, 2016</ref><ref name="signsandsymptomsofmyelofibrosiswiki1">Signs and symptoms of myelofibrosis. Wikipedia 2016. https://en.wikipedia.org/wiki/Myelofibrosis. Accessed on March 7, 2016</ref><ref name="cancercanadiansymptomsidiopathicmyelofibrosis1">Symptoms of idiopathic myelofibrosis. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/leukemia/leukemia/idiopathic-myelofibrosis/?region=on. Accessed on March 9, 2016</ref><ref name="symptoimmfgovcNCER1">Symptoms of primary myelofibrosis include pain below the ribs on the left side and feeling very tired. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/patient/chronic-treatment-pdq#section/_234. Accessed on March 10, 2016</ref> Common physical examination findings of myelofibrosis include [[pallor]], [[petechiae]], [[lymphadenopathy]], [[hepatomegaly]], and [[splenomegaly]].<ref name="symptoimmfgovcNCER1">Symptoms of primary myelofibrosis include pain below the ribs on the left side and feeling very tired. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/patient/chronic-treatment-pdq#section/_234. Accessed on March 10, 2016</ref> Laboratory findings consistent with the diagnosis of myelofibrosis include [[anemia|decreased red blood cells]], [[normochromic]] normocytic [[anemia]], tear-drop shaped RBCs, [[thrombocytopenia]], and raised levels of [[lactate dehydrogenase]].<ref name="wikidiagn1osismf1">Diagnosis of myelofibrosis. Wikipedia 2016. https://en.wikipedia.org/wiki/Myelofibrosis. Accessed on March 8, 2016</ref><ref name="cancercaidiopathicmyelofibrosisdx1">Diagnosis of idiopathic myelofibrosis. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/leukemia/leukemia/idiopathic-myelofibrosis/?region=on. Accessed on March 9, 2016</ref> X-ray may be helpful in the diagnosis of myelofibrosis. Findings on x-ray suggestive of myelofibrosis include [[osteosclerosis]] at different sites of the body, which tends to be diffuse and devoid of architectural distortion.<ref name="radiographicfeaturesofprimarymf1radiopaedia1">Radiographic features of primary myelofibrosis. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/myelofibrosis. Accessed on March 10, 2016</ref> CT scan and MRI may be helpful in the diagnosis of myelofibrosis. Findings on CT scan suggestive of myelofibrosis include [[bone sclerosis|diffuse bone sclerosis]].<ref name="radioctmf1">Radiographic features of myelofibrosis. Radswiki. Radiopaedia 2016. http://radiopaedia.org/cases/myelofibrosis. Accessed on March 14, 2016</ref> Findings on MRI suggestive of myelofibrosis include diffuse decrease bone marrow signal intensity.<ref name="radiomf1">Radiographic features of myelofibrosis. Radswiki. Radiopaedia 2016. http://radiopaedia.org/cases/myelofibrosis-1. Accessed on March 14, 2016</ref> Bone marrow biopsy is the imaging modality of choice for myelofibrosis. A bone marrow biopsy will reveal collagen fibrosis that has replaced the bone marrow.<ref name="wikidiagn1osismf1">Diagnosis of myelofibrosis. Wikipedia 2016. https://en.wikipedia.org/wiki/Myelofibrosis. Accessed on March 8, 2016</ref> Other diagnostic studies for myelofibrosis include ''[[JAK2]]'' mutation analysis testing and [[bone scan]].<ref name="radiographicfeaturesofprimarymf1radiopaedia1">Radiographic features of primary myelofibrosis. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/myelofibrosis. Accessed on March 10, 2016</ref> Red blood cell transfusion, [[danazol]] therapy, or [[thalidomide]] are recommended for patients who develop anemia. [[Ruxolitinib]], an inhibitor of ''[[JAK1]]'' and ''[[JAK2]]'', can reduce the [[splenomegaly]] and the debilitating symptoms of [[weight loss]], [[fatigue]], and [[night sweats]] for patients with ''JAK2''-positive or ''JAK2''-negative primary myelofibrosis, post–essential thrombocythemia myelofibrosis, or post–polycythemia vera myelofibrosis.<ref name="treatmentoverviewofmyelofibrosis1">Treatment overview of primary myelofibrosis. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_9. Accessed on March 10, 2016</ref> Hydroxyurea, [[chemotherapy]], [[radiotherapy]], or [[splenectomy]] are recommended for patients who develop splenomegaly.<ref name="treatmentoverviewofmyelofibrosis1">Treatment overview of primary myelofibrosis. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_9. Accessed on March 10, 2016</ref> [[Surgery]] is not the first-line treatment option for patients with myelofibrosis. [[Splenectomy]] is usually reserved for patients with massive splenectomy unresponsive to conservative treatment. The only known cure is allogeneic [[stem cell transplantation]], but this approach involves significant risks.<ref name="pmid15725078">{{cite journal |author=Cervantes F |title=Modern management of myelofibrosis |journal=Br. J. Haematol. |volume=128 |issue=5 |pages=583–92 |year=2005 |month=March |pmid=15725078 |doi=10.1111/j.1365-2141.2004.05301.x |url=http://dx.doi.org/10.1111/j.1365-2141.2004.05301.x}}</ref>
Myelofibrosis, a myeloproliferative disorder, is a condition in which the bone marrow is replaced with [[collagen|collagenous connective tissue]] and progressive [[fibrosis]], replacing the bone marrow with a scar tissue and hence disrupting the normal production of blood cells which leads to pancytopenia.<ref name="pmid27539616">{{cite journal |vauthors=Shantzer L, Berger K, Pu JJ |title=Primary myelofibrosis and its targeted therapy |journal=Ann. Hematol. |volume=96 |issue=4 |pages=531–535 |date=April 2017 |pmid=27539616 |doi=10.1007/s00277-016-2785-9 |url=}}</ref> The term myelofibrosis alone usually refers to primary myelofibrosis (PMF), also known as chronic idiopathic myelofibrosis (CIMF); the terms idiopathic and primary mean that the disease is of unknown or spontaneous origin. This is in contrast with myelofibrosis that develops secondary to [[polycythemia vera]], [[essential thrombocythemia]], [[leukemia]], or [[lymphoma]] (secondary myelofibrosis). It can develop as a result of mutations in JAK2, MPL, and CALR  genes.


==Historical Perspective==
==Historical Perspective==

Revision as of 20:15, 7 November 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]

Overview

Myelofibrosis, a myeloproliferative disorder, is a condition in which the bone marrow is replaced with collagenous connective tissue and progressive fibrosis, replacing the bone marrow with a scar tissue and hence disrupting the normal production of blood cells which leads to pancytopenia.[1] The term myelofibrosis alone usually refers to primary myelofibrosis (PMF), also known as chronic idiopathic myelofibrosis (CIMF); the terms idiopathic and primary mean that the disease is of unknown or spontaneous origin. This is in contrast with myelofibrosis that develops secondary to polycythemia vera, essential thrombocythemia, leukemia, or lymphoma (secondary myelofibrosis). It can develop as a result of mutations in JAK2, MPL, and CALR genes.

Historical Perspective

Myelofibrosis was first discribed by Gustav Heuck, a German surgeon, in 1879, under the title of 'Two cases of leukemia with peculiar blood and bone marrow findings'.[2]

Classification

Based on the origin, myelofibrosis may be classified into two subtypes: primary and secondary.[3]

Pathophysiology

Myelofibrosis is a clonal neoplastic disorder of hematopoiesis, the formation of blood cellular components.[4] It is one of the myleoproliferative disorders, diseases of the bone marrow in which excess cells are produced. Genes involved in the pathogenesis of myelofibrosis include JAK2, CALR, and MPL.[5]

Causes

Common causes of myelofibrosis include genetic mutations. The genes involved are listed here.[5][6][7]

Differentiating Myelofibrosis from other Diseases

Myelofibrosis must be differentiated from other diseases that cause diffuse bone sclerosis, such as sickle cell disease, hyperthyroidism, sclerosing bone dysplasia, osteoblastic metastases, and Paget's disease.[8][9] Myelofibrosis must be differentiated from other diseases that cause splenomegaly, such as anemia, CML, polycythemia rubra vera, cirrhosis, infections, neoplastic, and lipid storage disorders.[8][10]

Epidemiology and Demographics

The prevalence of myelofibrosis is approximately 1 per 100,000 individuals worldwide. Myelofibrosis is a disease that tends to affect the middle-aged and elderly population. The mean age at diagnosis is 60 years.[11] Males are more commonly affected with myelofibrosis than females. The male to female ratio is approximately 1.5 to 1.[12] Myelofibrosis usually affects individuals of the Ashkenazi Jews race. African American, Latin American, and Asian individuals are less likely to develop myelofibrosis.[13]

Risk Factors

Common risk factors in the development of myelofibrosis may be age, other myeloproliferative disorders, radiation, or industrial chemical exposure.[14]

Natural History, Complications and Prognosis

Myelofibrosis has a very indolent course.[15] If left untreated, myelofibrosis may progress to develop acute myelogenous leukemia, thrombohemorrhagic events, and progressive marrow failure. Common complications of myelofibrosis include infections, bleeding, hepatic failure, heart failure, and gout.[16][17][18][19][20] Prognosis is generally poor and the median survival for myelofibrosis is 3.5 years to 5.5 years, but patients younger than 55 years have a median survival of 11 years.[19]

Diagnosis

Diagnostic Criteria

According to the World Health Organization (WHO) diagnostic criteria for primary myelofibrosis, polycythemia vera, and essential thrombocythemia, the diagnosis of primary myelofibrosis is made when all three of the following major diagnostic criteria and at least two minor criteria are met.[21][22]

Staging

There is no established system for the staging of myelofibrosis.[19]

Symptoms

Symptoms of myelofibrosis include left upper quadrant abdominal pain, bruising, easy bleeding, pale skin, and frequent infections.[23][17][24][25]

Physical Examination

Common physical examination findings of myelofibrosis include pallor, petechiae, lymphadenopathy, hepatomegaly, and splenomegaly.[25]

Laboratory Findings

Laboratory findings consistent with the diagnosis of myelofibrosis include decreased red blood cells, normochromic normocytic anemia, tear-drop shaped RBCs, thrombocytopenia, and raised levels of lactate dehydrogenase.[15][26]

X Ray

X-ray may be helpful in the diagnosis of myelofibrosis. Findings on x-ray suggestive of myelofibrosis include osteosclerosis at different sites of the body, which tends to be diffuse and devoid of architectural distortion.[27]

CT

CT scan may be helpful in the diagnosis of myelofibrosis. Findings on CT scan suggestive of myelofibrosis include diffuse bone sclerosis.[28]

MRI

MRI may be helpful in the diagnosis of myelofibrosis. Findings on MRI suggestive of myelofibrosis include diffuse decrease bone marrow signal intensity.[29]

Bone Marrow Biopsy

Bone marrow biopsy is the imaging modality of choice for myelofibrosis. A bone marrow biopsy will reveal collagen fibrosis that has replaced the bone marrow.[15]

Other Imaging Findings

There are no other imaging findings associated with myelofibrosis.

Other Diagnostic Studies

Other diagnostic studies for myelofibrosis include JAK2 mutation analysis testing and bone scan.[27]

Treatment

Medical Therapy

Red blood cell transfusion, danazol therapy, or thalidomide are recommended for patients who develop anemia. Ruxolitinib, an inhibitor of JAK1 and JAK2, can reduce the splenomegaly and the debilitating symptoms of weight loss, fatigue, and night sweats for patients with JAK2-positive or JAK2-negative primary myelofibrosis, post–essential thrombocythemia myelofibrosis, or post–polycythemia vera myelofibrosis.[30] Hydroxyurea, chemotherapy, radiotherapy, or splenectomy are recommended for patients who develop splenomegaly.[30]

Surgery

Surgery is not the first-line treatment option for patients with myelofibrosis. Splenectomy is usually reserved for patients with massive splenectomy unresponsive to conservative treatment. The only known cure is allogeneic stem cell transplantation, but this approach involves significant risks.[31]

Prevention

There are no primary or secondary preventive measures available for myelofibrosis.[32]

References

  1. ↑ Shantzer L, Berger K, Pu JJ (April 2017). "Primary myelofibrosis and its targeted therapy". Ann. Hematol. 96 (4): 531–535. doi:10.1007/s00277-016-2785-9. PMID 27539616.
  2. ↑ Tefferi, A (2007). "The history of myeloproliferative disorders: before and after Dameshek". Leukemia. 22 (1): 3–13. doi:10.1038/sj.leu.2404946. ISSN 0887-6924.
  3. ↑ Classification of myelofibrosis. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/myelofibrosis. Accessed on March 14, 2016
  4. ↑ Causes of myelofibrosis. Wikipedia 2016. https://en.wikipedia.org/wiki/Myelofibrosis. Accessed on March 7, 2016
  5. ↑ 5.0 5.1 Tefferi, A; Lasho, T L; Finke, C M; Knudson, R A; Ketterling, R; Hanson, C H; Maffioli, M; Caramazza, D; Passamonti, F; Pardanani, A (2014). "CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons". Leukemia. 28 (7): 1472–1477. doi:10.1038/leu.2014.3. ISSN 0887-6924.
  6. ↑ Baxter EJ, Scott LM, Campbell PJ; et al. (2005). "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders". Lancet. 365 (9464): 1054–61. doi:10.1016/S0140-6736(05)71142-9. PMID 15781101.
  7. ↑ Pikman Y, Lee BH, Mercher T; et al. (2006). "MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia". PLoS Med. 3 (7): e270. doi:10.1371/journal.pmed.0030270. PMC 1502153. PMID 16834459. Unknown parameter |month= ignored (help)
  8. ↑ 8.0 8.1 Differential diagnosis of myelofibrosis. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/myelofibrosis. Accessed on March 10, 2016
  9. ↑ Diffuse bony sclerosis: differential diagnosis. Dr Craig Hacking and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/diffuse-bony-sclerosis-differential-diagnosis. Accessed on March 10, 2016
  10. ↑ Splenomegaly. Dr Henry Knipe and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/Italic textarticles/splenomegaly. Accessed on March 11, 2016
  11. ↑ Epidemiology of myelofibrosis. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/myelofibrosis. Accessed on March 8, 2016
  12. ↑ Tefferi A, Lasho TL, Jimma T, Finke CM, Gangat N, Vaidya R; et al. (2012). "One thousand patients with primary myelofibrosis: the mayo clinic experience". Mayo Clin Proc. 87 (1): 25–33. doi:10.1016/j.mayocp.2011.11.001. PMC 3538387. PMID 22212965.
  13. ↑ Causes. The physician's guide to myelofibrosis 2016. http://nordphysicianguides.org/wp-content/uploads/2012/11/NORD_Physician_Guide_to_Myelofibrosis.pdf. Accessed on March 14, 2016
  14. ↑ Risk factors for myelofibrosis. Mayo clinic 2016. http://www.mayoclinic.org/diseases-conditions/myelofibrosis/basics/risk-factors/con-20027210. Accessed on March 7, 2016
  15. ↑ 15.0 15.1 15.2 Diagnosis of myelofibrosis. Wikipedia 2016. https://en.wikipedia.org/wiki/Myelofibrosis. Accessed on March 8, 2016
  16. ↑ Complications of myelofibrosis. US National Library of Medicine 2016. https://www.nlm.nih.gov/medlineplus/ency/article/000531.htm. Accessed on March 7, 2016
  17. ↑ 17.0 17.1 Signs and symptoms of myelofibrosis. Wikipedia 2016. https://en.wikipedia.org/wiki/Myelofibrosis. Accessed on March 7, 2016
  18. ↑ Kelle, Bayram; Yıldız, Fatih; Paydas, Semra; Bagır, Emine Kılıc; Ergin, Melek; Kozanoglu, Erkan (2015). "Coexistence of hypertrophic osteoarthropathy and myelofibrosis". Revista Brasileira de Reumatologia (English Edition). doi:10.1016/j.rbre.2014.11.004. ISSN 2255-5021.
  19. ↑ 19.0 19.1 19.2 Disease overview of primary myelofibrosis. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_9. Accessed on March 10, 2016
  20. ↑ Complications of primary myelofibrosis. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/myelofibrosis. Accessed on March 10, 2016
  21. ↑ World Health Organization (WHO) Diagnostic Criteria for Primary Myelofibrosis (PMF), Polycythemia Vera (PV), and Essential Thrombocythemia (ET). MPN Connect 2016. http://www.mpnconnect.com/pdf/who-diagnostic-criteria-myelofibrosis.pdf. Accessed on March 8, 2016
  22. ↑ Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA; et al. (2007). "Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel". Blood. 110 (4): 1092–7. doi:10.1182/blood-2007-04-083501. PMID 17488875.
  23. ↑ Symptoms of myelofibrosis. US National Library of Medicine 2016. https://www.nlm.nih.gov/medlineplus/ency/article/000531.htm. Accessed on March 7, 2016
  24. ↑ Symptoms of idiopathic myelofibrosis. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/leukemia/leukemia/idiopathic-myelofibrosis/?region=on. Accessed on March 9, 2016
  25. ↑ 25.0 25.1 Symptoms of primary myelofibrosis include pain below the ribs on the left side and feeling very tired. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/patient/chronic-treatment-pdq#section/_234. Accessed on March 10, 2016
  26. ↑ Diagnosis of idiopathic myelofibrosis. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/leukemia/leukemia/idiopathic-myelofibrosis/?region=on. Accessed on March 9, 2016
  27. ↑ 27.0 27.1 Radiographic features of primary myelofibrosis. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/myelofibrosis. Accessed on March 10, 2016
  28. ↑ Radiographic features of myelofibrosis. Radswiki. Radiopaedia 2016. http://radiopaedia.org/cases/myelofibrosis. Accessed on March 14, 2016
  29. ↑ Radiographic features of myelofibrosis. Radswiki. Radiopaedia 2016. http://radiopaedia.org/cases/myelofibrosis-1. Accessed on March 14, 2016
  30. ↑ 30.0 30.1 Treatment overview of primary myelofibrosis. National cancer institute 2016. http://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_9. Accessed on March 10, 2016
  31. ↑ Cervantes F (2005). "Modern management of myelofibrosis". Br. J. Haematol. 128 (5): 583–92. doi:10.1111/j.1365-2141.2004.05301.x. PMID 15725078. Unknown parameter |month= ignored (help)
  32. ↑ Prevention of myelofibrosis. US National Library of Medicine 2016. https://www.nlm.nih.gov/medlineplus/ency/article/000531.htm. Accessed on March 7, 2016


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