Myelofibrosis causes

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

Overview

Myelofibrosis is most commonly caused by somatic mutations in the myeloproliferative leukemia virus (MPL) oncogene, the calreticulin (CALR) gene, or Janus kinase 2 (JAK2) gene. Less common mutations in other genes have also been documented. It can also be the result of other primary disorders manifesting as a complication or part of the disease process. Infections, malignancies, hematologic disorders, autoimmune diseases and exposure to certain toxins can also cause myelofibrosis.

Causes

Life-threatening Causes

There are no life-threatening causes of myelofibrosis, however complications resulting from untreated myelofibrosis is common.

Common Causes

Common causes of myelofibrosis include:

  • Genetic mutations in:

Less Common Causes

Genetic Causes

Common

Myelofibrosis is commonly caused by mutations in the following genes:

Less Common

Myelofibrosis is less-commonly caused by mutations in the following genes:

Causes by Organ System

Cardiovascular No underlying causes
Chemical/Poisoning benzene, thorium dioxide, nitrosurea[30][31][32][33][34][35][36][37]
Dental No underlying causes
Dermatologic No underlying causes
Drug Side Effect No underlying causes
Ear Nose Throat No underlying causes
Endocrine Primary hyperparathyroidism[38]
Environmental benzene, nitrosurea[30][31][32][33][34]
Gastroenterologic No underlying causes
Genetic Mutations in multiple genes discussed above
Hematologic Essential thrombocythemia (ET), Polycythemia vera (PV), and Multiple myeloma (MM)[16][17][18][19][20][21]
Iatrogenic No underlying causes
Infectious Disease tuberculosis (TB), HIV infection, and dengue fever[22][23][24][25]
Musculoskeletal/Orthopedic No underlying causes
Neurologic No underlying causes
Nutritional/Metabolic No underlying causes
Obstetric/Gynecologic No underlying causes
Oncologic Hodgkin's lymphoma, Non-Hodgkin lymphoma, and Bone metastases[12][13][14][15][40]
Ophthalmologic No underlying causes
Overdose/Toxicity No underlying causes
Psychiatric No underlying causes
Pulmonary No underlying causes
Renal/Electrolyte No underlying causes
Rheumatology/Immunology/Allergy No underlying causes
Sexual No underlying causes
Trauma No underlying causes
Urologic No underlying causes
Miscellaneous x- or γ-radiation exposure

References

  1. ↑ 1.0 1.1 1.2 1.3 Tefferi A (December 2016). "Primary myelofibrosis: 2017 update on diagnosis, risk-stratification, and management". Am. J. Hematol. 91 (12): 1262–1271. doi:10.1002/ajh.24592. PMID 27870387.
  2. ↑ 2.0 2.1 2.2 2.3 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.
  3. ↑ 3.0 3.1 3.2 3.3 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.
  4. ↑ 4.0 4.1 4.2 4.3 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)
  5. ↑ 5.0 5.1 5.2 5.3 Alshemmari SH, Rajan R, Emadi A (2016). "Molecular Pathogenesis and Clinical Significance of Driver Mutations in Primary Myelofibrosis: A Review". Med Princ Pract. 25 (6): 501–509. doi:10.1159/000450956. PMC 5588514. PMID 27756071.
  6. ↑ 6.0 6.1 6.2 6.3 Shammo JM, Stein BL (December 2016). "Mutations in MPNs: prognostic implications, window to biology, and impact on treatment decisions". Hematology Am Soc Hematol Educ Program. 2016 (1): 552–560. doi:10.1182/asheducation-2016.1.552. PMC 6142495. PMID 27913528.
  7. ↑ 7.0 7.1 7.2 7.3 Li B, Xu J, Wang J, Gale RP, Xu Z, Cui Y, Yang L, Xing R, Ai X, Qin T, Zhang Y, Zhang P, Xiao Z (November 2014). "Calreticulin mutations in Chinese with primary myelofibrosis". Haematologica. 99 (11): 1697–700. doi:10.3324/haematol.2014.109249. PMC 4222480. PMID 24997152.
  8. ↑ 8.0 8.1 8.2 8.3 Rotunno G, Pacilli A, Artusi V, Rumi E, Maffioli M, Delaini F, Brogi G, Fanelli T, Pancrazzi A, Pietra D, Bernardis I, Belotti C, Pieri L, Sant'Antonio E, Salmoiraghi S, Cilloni D, Rambaldi A, Passamonti F, Barbui T, Manfredini R, Cazzola M, Tagliafico E, Vannucchi AM, Guglielmelli P (July 2016). "Epidemiology and clinical relevance of mutations in postpolycythemia vera and postessential thrombocythemia myelofibrosis: A study on 359 patients of the AGIMM group". Am. J. Hematol. 91 (7): 681–6. doi:10.1002/ajh.24377. PMID 27037840.
  9. ↑ 9.0 9.1 9.2 9.3 Song J, Hussaini M, Zhang H, Shao H, Qin D, Zhang X, Ma Z, Hussnain Naqvi SM, Zhang L, Moscinski LC (May 2017). "Comparison of the Mutational Profiles of Primary Myelofibrosis, Polycythemia Vera, and Essential Thrombocytosis". Am. J. Clin. Pathol. 147 (5): 444–452. doi:10.1093/ajcp/aqw222. PMC 5402718. PMID 28419183.
  10. ↑ 10.0 10.1 10.2 10.3 Vannucchi AM, Lasho TL, Guglielmelli P, Biamonte F, Pardanani A, Pereira A, Finke C, Score J, Gangat N, Mannarelli C, Ketterling RP, Rotunno G, Knudson RA, Susini MC, Laborde RR, Spolverini A, Pancrazzi A, Pieri L, Manfredini R, Tagliafico E, Zini R, Jones A, Zoi K, Reiter A, Duncombe A, Pietra D, Rumi E, Cervantes F, Barosi G, Cazzola M, Cross NC, Tefferi A (September 2013). "Mutations and prognosis in primary myelofibrosis". Leukemia. 27 (9): 1861–9. doi:10.1038/leu.2013.119. PMID 23619563.
  11. ↑ 11.0 11.1 11.2 11.3 Tefferi A, Pardanani A (April 2015). "Myeloproliferative Neoplasms: A Contemporary Review". JAMA Oncol. 1 (1): 97–105. doi:10.1001/jamaoncol.2015.89. PMID 26182311.
  12. ↑ 12.0 12.1 Boiocchi L, Mathew S, Gianelli U, Iurlo A, Radice T, Barouk-Fox S, Knowles DM, Orazi A (December 2013). "Morphologic and cytogenetic differences between post-polycythemic myelofibrosis and primary myelofibrosis in fibrotic stage". Mod. Pathol. 26 (12): 1577–85. doi:10.1038/modpathol.2013.109. PMID 23787440.
  13. ↑ 13.0 13.1 Sakatoku K, Takeoka Y, Araki T, Miura A, Fujitani Y, Yamamura R, Miyagi Y, Senzaki H, Ohta K (2017). "Lymphocyte-depleted classical Hodgkin lymphoma accompanied by myelofibrosis". Rinsho Ketsueki (in Japanese). 58 (7): 772–775. doi:10.11406/rinketsu.58.772. PMID 28781273.
  14. ↑ 14.0 14.1 Fu R, Yu H, Wu YH, Liu H, Shao ZH (September 2015). "Hodgkin's lymphoma associated with myelofibrosis: A case report". Oncol Lett. 10 (3): 1551–1554. doi:10.3892/ol.2015.3438. PMC 4533276. PMID 26622707.
  15. ↑ 15.0 15.1 Liu YL, Wang WJ, Wang XN (June 2015). "[Pathological Characteristics of Bone Marrow in Non-Hodgkin's Lymphoma Patients with Secondary Myelofibrosis and Their Relationship with Prognosis]". Zhongguo Shi Yan Xue Ye Xue Za Zhi (in Chinese). 23 (3): 674–8. doi:10.7534/j.issn.1009-2137.2015.03.014. PMID 26117015.
  16. ↑ 16.0 16.1 16.2 Dolgikh TY, Domnikova NP, Tornuev YV, Vinogradova EV, Krinitsyna YM (February 2017). "Incidence of Myelofibrosis in Chronic Myeloid Leukemia, Multiple Myeloma, and Chronic Lymphoid Leukemia during Various Phases of Diseases". Bull. Exp. Biol. Med. 162 (4): 483–487. doi:10.1007/s10517-017-3645-x. PMID 28239786.
  17. ↑ 17.0 17.1 Zhao J, Ma L, Guan JH (August 2017). "[Pathological Characteristics of Bone Marrow in Multiple Myeloma Patients with Secondary Myelofibrosis and Their Relationship with Prognosis]". Zhongguo Shi Yan Xue Ye Xue Za Zhi (in Chinese). 25 (4): 1080–1085. doi:10.7534/j.issn.1009-2137.2017.04.021. PMID 28823272.
  18. ↑ 18.0 18.1 Passamonti F, Giorgino T, Mora B, Guglielmelli P, Rumi E, Maffioli M, Rambaldi A, Caramella M, Komrokji R, Gotlib J, Kiladjian JJ, Cervantes F, Devos T, Palandri F, De Stefano V, Ruggeri M, Silver RT, Benevolo G, Albano F, Caramazza D, Merli M, Pietra D, Casalone R, Rotunno G, Barbui T, Cazzola M, Vannucchi AM (December 2017). "A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis". Leukemia. 31 (12): 2726–2731. doi:10.1038/leu.2017.169. PMID 28561069.
  19. ↑ 19.0 19.1 Masarova L, Bose P, Daver N, Pemmaraju N, Newberry KJ, Manshouri T, Cortes J, Kantarjian HM, Verstovsek S (August 2017). "Patients with post-essential thrombocythemia and post-polycythemia vera differ from patients with primary myelofibrosis". Leuk. Res. 59: 110–116. doi:10.1016/j.leukres.2017.06.001. PMC 5573611. PMID 28601551.
  20. ↑ 20.0 20.1 MARKAND ON (May 1965). "SECONDARY MARBLE BONE DISEASE: GENERALISED OSTEOSCLEROSIS AND MYELOFIBROSIS IN CARCINOMA OF PROSTATE WITH A CASE REPORT". J Assoc Physicians India. 13: 349–55. PMID 14302719.
  21. ↑ 21.0 21.1 Chang JC, Naqvi T (2003). "Thrombotic thrombocytopenic purpura associated with bone marrow metastasis and secondary myelofibrosis in cancer". Oncologist. 8 (4): 375–80. PMID 12897334.
  22. ↑ 22.0 22.1 Qing X, Sun N, Yeh J, Yue C, Cai J (October 2014). "Dengue fever and bone marrow myelofibrosis". Exp. Mol. Pathol. 97 (2): 208–10. doi:10.1016/j.yexmp.2014.07.004. PMID 25016180.
  23. ↑ 23.0 23.1 Lee AC, Fong CM (May 2012). "Autoimmune myelofibrosis as the first manifestation of human immunodeficiency virus infection in an infant". Ann. Hematol. 91 (5): 809–810. doi:10.1007/s00277-011-1329-6. PMID 21894472.
  24. ↑ 24.0 24.1 Hashim MS, Kordofani AY, el Dabi MA (March 1997). "Tuberculosis and myelofibrosis in children: a report". Ann Trop Paediatr. 17 (1): 61–5. PMID 9176580.
  25. ↑ 25.0 25.1 Viallard JF, Parrens M, Boiron JM, Texier J, Mercie P, Pellegrin JL (June 2002). "Reversible myelofibrosis induced by tuberculosis". Clin. Infect. Dis. 34 (12): 1641–3. doi:10.1086/340524. PMID 12032901.
  26. ↑ Jain N, Sinha R, Sengupta J, Chakrabartty J (June 2016). "A rare case of myelofibrosis secondary to juvenile idiopathic arthritis". Br. J. Haematol. 173 (6): 819. doi:10.1111/bjh.14106. PMID 27102067.
  27. ↑ Cansu DÜ, Teke HÜ, Korkmaz C (March 2017). "A rare cause of cytopenia in a patient with systemic lupus erythematosus: Autoimmune myelofibrosis". Eur J Rheumatol. 4 (1): 76–78. doi:10.5152/eurjrheum.2016.011. PMC 5335895. PMID 28293461.
  28. ↑ Thorsteinsdottir S, Bjerrum OW, Hasselbalch HC (2013). "Myeloproliferative neoplasms in five multiple sclerosis patients". Leuk Res Rep. 2 (2): 61–3. doi:10.1016/j.lrr.2013.06.004. PMC 3850374. PMID 24371783.
  29. ↑ Abaza Y, Yin CC, Bueso-Ramos CE, Wang SA, Verstovsek S (April 2017). "Primary autoimmune myelofibrosis: a case report and review of the literature". Int. J. Hematol. 105 (4): 536–539. doi:10.1007/s12185-016-2129-5. PMID 27830539.
  30. ↑ 30.0 30.1 30.2 Bausà R, Navarro L, Cortès-Franch I (2017). "[Myelofibrosis in a benzene-exposed cleaning worker]". Arch Prev Riesgos Labor (in Spanish; Castilian). 20 (3): 167–169. doi:10.12961/aprl.2017.20.3.03. PMID 28715625.
  31. ↑ 31.0 31.1 31.2 Hu H (January 1987). "Benzene-associated myelofibrosis". Ann. Intern. Med. 106 (1): 171–2. PMID 3789571.
  32. ↑ 32.0 32.1 32.2 Tondel M, Persson B, Carstensen J (February 1995). "Myelofibrosis and benzene exposure". Occup Med (Lond). 45 (1): 51–2. PMID 7703476.
  33. ↑ 33.0 33.1 33.2 Visfeldt J, Andersson M (January 1995). "Pathoanatomical aspects of malignant haematological disorders among Danish patients exposed to thorium dioxide". APMIS. 103 (1): 29–36. PMID 7695889.
  34. ↑ 34.0 34.1 34.2 Brandt L, Emanuelsson H, Mitelman F, Stenstam M, Söderström N (1977). "Pronounced deficiency in T-cells and lymphocyte chromosomal aberrations in a patient with sarcoidosis, myelofibrosis and acute leukaemia following thorotrast angiography". Acta Med Scand. 201 (5): 487–9. PMID 302634.
  35. ↑ 35.0 35.1 Arnold AG, Oelbaum MH (February 1980). "Thorotrast administration followed by myelofibrosis". Postgrad Med J. 56 (652): 124–7. PMC 2425512. PMID 7393792.
  36. ↑ 36.0 36.1 Jennings RC, Priestley SE (December 1978). "Haemangioendothelioma (Kupffer cell angiosarcoma), myelofibrosis, splenic atrophy, and myeloma paraproteinaemia after parenteral thorotrast administration". J. Clin. Pathol. 31 (12): 1125–32. PMC 1145517. PMID 748384.
  37. ↑ 37.0 37.1 McKenney SA, Fehir KM (October 1986). "Myelofibrosis following treatment with a nitrosourea for malignant glioma". Cancer. 58 (7): 1426–7. PMID 3742462.
  38. ↑ 38.0 38.1 Lim DJ, Oh EJ, Park CW, Kwon HS, Hong EJ, Yoon KH, Kang MI, Cha BY, Lee KW, Son HY, Kang SK (December 2007). "Pancytopenia and secondary myelofibrosis could be induced by primary hyperparathyroidism". Int J Lab Hematol. 29 (6): 464–8. doi:10.1111/j.1365-2257.2006.00877.x. PMID 17988303.
  39. ↑ 39.0 39.1 39.2 39.3 39.4 39.5 39.6 39.7 39.8 Patel KP, Newberry KJ, Luthra R, Jabbour E, Pierce S, Cortes J, Singh R, Mehrotra M, Routbort MJ, Luthra M, Manshouri T, Santos FP, Kantarjian H, Verstovsek S (August 2015). "Correlation of mutation profile and response in patients with myelofibrosis treated with ruxolitinib". Blood. 126 (6): 790–7. doi:10.1182/blood-2015-03-633404. PMC 4528066. PMID 26124496.
  40. ↑ Hiwada K, Sera Y, Nishimura M (July 1970). "[Autopsy case of secondary myelofibrosis due to bone marrow metastasis of stomach cancer]". Iryo (in Japanese). 24 (7): 585–90. PMID 5458299.



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