İstanbul Tıp Fakültesi Dergisi

GÖNDERBİLGİ
EnglishTürkçe

Derleme


DOI :https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77   IUP :https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77    Tam Metin (PDF)

PRİMER MİYELOFİBROZİS: PATOGENEZ, TEŞHİS VE TEDAVİDE GÜNCEL BİLGİLER

İpek Yönal Hindilerden, Fatma Deniz Sargın

Primer miyelofibrozis (PMF), anemi, periferik kan yaymasında ‘tear drop’ şeklinde eritrositler, lökoeritroblastozis, kemik iliği fibrozisi, osteosklerozis ve ekstramedüller hematopoez ile karakterize miyeloproliferatif neoplazilerden (MPN) biridir. JAK2V617F mutasyonu PMF olgularının yaklaşık %50’sinde ve MPL mutasyonları %10’unda görülmektedir. PMF’in hücresel fazında kemik iliği biyopsisi atipik megakaryositler ve belirgin olmayan kemik iliği fibrozisi ile birlikte hiperselüler kemik iliğini ortaya çıkarır. PMF tanısı için diğer MPN’lerin dışlanması gerekmektedir. Birçok hasta PMF’in fibrotik fazında tanı alır. Bu fazdaki hastalarda fibrozis, tipik olarak yoğun retikülin lif artışı şeklinde ortaya çıkmakla beraber sonrasında sıklıkla kollagen fibrozisi gözlenir. Ortalama yaşam süresi yaklaşık 5 yıldır. PMF’in yaklaşık %20’sinde ortaya çıkan lösemik transformasyon, ölümün başlıca nedenidir. Diğer ölüm nedenleri arasında kardiyovasküler hastalıklar gibi komorbid hastalıklar yanında sitopeniye bağlı ortaya çıkan enfeksiyonlar ve kanama vardır. PMF için birkaç prognostik skorlama sistemi geliştirilmiştir (örneğin IPSS, DIPSS, DIPSS Plus). PMF’deki somatik mutasyonların prognostik önemi araştırılmıştır. ASXL1, SRSF2 ve EZH2 mutasyonlarının kısa yaşam süresi ile ilişkili bağımsız faktörler olduğu ve IDH1, IDH2, SRSF2 ve ASXL1 mutasyonlarının lösemi ilişkisiz sağkalımı (LFS) kısalttığı bildirilmiştir. Sonuç olarak PMF’de ASXL1, EZH2, SRSF2 ve IDH mutasyonlarının lösemik transformasyon veya ölüm riskini belirlemede yararlı olabileceği söylenebilir. Günümüzde bu moleküler belirteçler yoğun araştırma konusudur. PMF’de tek küratif tedavi yöntemi allogeneik hematopoetik kök hücre nakli (AHKHN) olmasına rağmen tedavi ile ilişkili mortalite oranı yüksektir. AHKHN dışındaki diğer tedavi şekilleri palyatif olup farklı etkinlik ve toksisiteye sahiptir. PMF’de tedavi yöntemlerini karşılaştıran az sayıda çalışma olduğundan, aralarından seçim yapılarak önerilmesi mümkün değildir. Bu derlemenin amacı, PMF tanılı olgularda patogenez, tanı yöntemleri ve güncel tedaviyi özetlemektir.

Anahtar Kelimeler: JAK2V617F mutasyonu, Miyeloproliferatif neoplaziler, MPL mutasyonları, Primer miyelofibrozis
DOI :https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77   IUP :https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77    Tam Metin (PDF)

PRIMARY MYELOFIBROSIS: UPDATE ON PATHOGENESIS, DIAGNOSIS AND MANAGEMENT

İpek Yönal Hindilerden, Fatma Deniz Sargın

Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm (MPN) characterized by anemia, teardropshaped red cells in blood, leukoerythroblastosis, bone marrow fibrosis, osteosclerosis and extramedullary hematopoiesis. Approximately 50% of PMF patients harbor JAK2V617F mutation and MPL mutations are present in a further 10%. Bone marrow examination reveals a hypercellular bone marrow with atypical megakaryocytes and slight marrow fibrosis in cellular phase of PMF. Diagnosis requires the exclusion of other MPN. Most patients are diagnosed in the fibrotic phase of PMF, when fibrosis is typically extensive with reticulin fibers and often subsequently accompanied by collagen fibrosis. Overall median survival is approximately 5 years. Death is mainly due to leukemic transformation, accounting for 20% of PMF patients. Others succumb to consequences of cytopenias such as infection or bleeding or to comorbid conditions including cardiovascular events. A number of prognostic scoring systems have been developed for PMF (eg. IPSS, DIPPS, DIPSS Plus). Analysis of a total of 879 patients included in a European and Mayo Clinic cohort showed that ASXL1, SRSF2 and EZH2 mutations independently predicted shortened survival. Leukemia-free survival (LFS) was negatively affected by IDH1/2, SRSF2, and ASXL1 mutations. Profiling for ASXL1, EZH2, SRSF2 and IDH mutations may identify PMF patients at risk for leukemic transformation or death. Currently, these molecular markers are mainly of research interest. Allogeneic hematopoietic stem cell transplantation (AHSCT) is the only curative treatment modality in PMF, yet it is associated with high treatment-related mortality. All other treatment modalities are palliative and show differences in efficacy and toxicity. There are few randomized trials comparing these modalities. Thus, it is not possible to make strong recommendations for selecting one treatment over another. This review aims to highlight the pathogenesis, diagnosis and current management in PMF.

Anahtar Kelimeler: JAK2V617F mutation, MPL mutations, Myeloproliferative neoplasms, Primary myelofibrosis

PDF Görünüm

Referanslar

  • 1. Ballen KK, Shrestha S, Sobocinski KA, Zhang MJ, Bashey A, Bolwell BJ, Cervantes F, Devine SM, Gale RP, Gupta V, Hahn TE, Hogan WJ, Kröger N, Litzow MR, Marks DI, Maziarz RT, McCarthy PL, Schiller G, Schouten HC, Roy V, Wiernik PH, Horowitz MM, Giralt SA, Arora M. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant. 2010;16(3):358-67. google scholar
  • 2. Barosi G. Myelofibrosis with myeloid metaplasia. Hematol Oncol Clin North Am. 2003;17(5):1211-26. google scholar
  • 3. Barosi G, Ambrosetti A, Centra A, Falcone A, Finelli C, Foa P, Grossi A, Guarnone R, Rupoli S, Luciano L, Petti MC, Pogliani E, Russo D, Ruggeri M, Quaglini S. Splenectomy and risk of blast transformation in myelofibrosis with myeloid metaplasia. Italian Cooperative Study Group on Myeloid with Myeloid Metaplasia. Blood. 1998;91(10):3630-6. google scholar
  • 4. Barosi G, Viarengo G, Pecci A, Rosti V, Piaggio G, Marchetti M, Frassoni F. Diagnostic and clinical relevance of the number of circulating CD34(+) cells in myelofibrosis with myeloid metaplasia. Blood. 2001;98(12):3249-55. google scholar
  • 5. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN, Green AR; Cancer Genome Project. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054-61. google scholar
  • 6. Begna KH, Mesa RA, Pardanani A, Hogan WJ, Litzow MR, McClure RF, Tefferi A. A phase-2 trial of low-dose pomalidomide in myelofibrosis. Leukemia. 2011 Feb;25(2):301-4. Epub 2010 Nov 5. google scholar
  • 7. Bench AJ, Nacheva EP, Champion KM, Green AR. Molecular genetics and cytogenetics of myeloproliferative disorders. Baillieres Clin Haematol. 1998;11(4):819-48. google scholar
  • 8. Bird GW, Wingham J, Richardson SG. Myelofibrosis, autoimmune haemolytic anaemia and Tn-polyagglutinability. Haematologia (Budap). 1985;18(2):99-103. google scholar
  • 9. Buhr T, Büsche G, Choritz H, Länger F, Kreipe H. Evolution of myelofibrosis in chronic idiopathic myelofibrosis as evidenced in sequential bone marrow biopsy specimens. Am J Clin Pathol. 2003;119(1):152-8. google scholar
  • 10.Buschle M, Janssen JW, Drexler H, Lyons J, Anger B, Bartram CR. Evidence for pluripotent stem cell origin of idiopathic myelofibrosis: clonal analysis of a case characterized by a N-ras gene mutation. Leukemia. 1988;2(10):658-60. google scholar
  • 11.Cappio FC, Vigliani R, Novarino A, Camussi G, Campana D, Gavosto F. Idiopathic myelofibrosis: a possible role for immune-complexes in the pathogenesis of bone marrow fibrosis. Br J Haematol. 1981;49(1):17-21. google scholar
  • 12.Caramazza D, Begna KH, Gangat N, Vaidya R, Siragusa S, Van Dyke DL, Hanson C, Pardanani A, Tefferi A. Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: a single center study of 433 patients. Leukemia. 2011;25(1):82-8. google scholar
  • 13.Carlo-Stella C, Cazzola M, Gasner A, Barosi G, Dezza L, Meloni F, Pedrazzoli P, Hoelzer D, Ascari E. Effects of recombinant alpha and gamma interferons on the in vitro growth of circulating hematopoietic progenitor cells (CFU-GEMM, CFUMk, BFU-E, and CFU-GM) from patients with myelofibrosis with myeloid metaplasia. Blood. 1987;70(4):1014-9. google scholar
  • 14.Castro-Malaspina H, Rabellino EM, Yen A, Nachman RL, Moore MA. Human megakaryocyte stimulation of proliferation of bone marrow fibroblasts. Blood. 1981;57(4):781-7. google scholar
  • 15.Cervantes F, Alvarez-Larrán A, Hernández-Boluda JC, Sureda A, Torrebadell M, Montserrat E. Erythropoietin treatment of the anaemia of myelofibrosis with myeloid metaplasia: results in 20 patients and review of the literature. Br J Haematol. 2004;127(4):399-403. Review. google scholar
  • 16.Cervantes F, Barosi G, Demory JL, Reilly J, Guarnone R, Dupriez B, Pereira A, Montserrat E. Myelofibrosis with myeloid metaplasia in young individuals: disease characteristics, prognostic factors and identification of risk groups. Br J Haematol. 1998;102(3):684-90. google scholar
  • 17.Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 2009;113:2895–2901. google scholar
  • 18.Cervantes F, Mesa R, Barosi G. New and old treatment modalities in primary myelofibrosis. Cancer J. 2007;13(6):377-83. google scholar
  • 19.Cox MC, Panetta P, Venditti A, Abruzzese E, Del Poeta G, Cantonetti M, Amadori S. New reciprocal translocation t(6;10) (q27;q11) associated with idiopathic myelofibrosis and eosinophilia. Leuk Res. 2001;25(4):349-51. google scholar
  • 20. Demory JL, Dupriez B, Fenaux P, Laï JL, Beuscart R, Jouet JP, Deminatti M, Bauters F. Cytogenetic studies and their prognostic significance in agnogenic myeloid metaplasia: a report on 47 cases. Blood. 1988;72(3):855-9. google scholar
  • 21. Dingli D, Grand FH, Mahaffey V, Spurbeck J, Ross FM, Watmore AE, Reilly JT, Cross NC, Dewald GW, Tefferi A. Der(6)t(1;6)(q21-23;p21.3): a specific cytogenetic abnormality in myelofibrosis with myeloid metaplasia. Br J Haematol. 2005;130(2):229-32. google scholar
  • 22. Eriksson KA, Sigvaldason A, Lindholm A, SafaiKutti S, Kutti J. Platelet activation in response to phlebotomy. An experimental study of healthy blood donors. Acta Med Scand. 1982;212(3):121-3. google scholar
  • 23. Gaidano G, Guerrasio A, Serra A, Carozzi F, Cambrin GR, Petroni D, Saglio G. Mutations in the P53 and RAS family genes are associated with tumor progression of BCR/ABL negative chronic myeloproliferative disorders. Leukemia. 1993;7(7):946-53. google scholar
  • 24. Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S, Van Dyke D, Hanson C, Wu W, Pardanani A, Cervantes F, Passamonti F, Tefferi A. DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol. 2011;29(4):392-7. google scholar
  • 25. Giraudier S, Chagraoui H, Komura E, Barnache S, Blanchet B, LeCouedic JP, Smith DF, Larbret F, Taksin AL, Moreau-Gachelin F, Casadevall N, Tulliez M, Hulin A, Debili N, Vainchenker W. Overexpression of FKBP51 in idiopathic myelofibrosis regulates the growth factor independence of megakaryocyte progenitors. Blood. 2002;100(8):2932-40. google scholar
  • 26. Guglielmelli P, Barosi G, Rambaldi A, Marchioli R, Masciulli A, Tozzi L, Biamonte F, Bartalucci N, Gattoni E, Lupo ML, Finazzi G, Pancrazzi A, Antonioli E, Susini MC, Pieri L, Malevolti E, Usala E, Occhini U, Grossi A, Caglio S, Paratore S, Bosi A, Barbui T, Vannucchi AM; AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM) investigators. Safety and efficacy of everolimus, a mTOR inhibitor, as single agent in a phase 1/2 study in patients with myelofibrosis. Blood. 2011;118(8):2069-76. google scholar
  • 27. Hernández JM, San Miguel JF, González M, Orfao A, Cañizo MC, Bascones C, Hernández J, López Borrasca A. Development of acute leukaemia after idiopathic myelofibrosis. J Clin Pathol. 1992;45(5):427-30. google scholar
  • 28. Huang J, Li CY, Mesa RA, Wu W, Hanson CA, Pardanani A, Tefferi A. Risk factors for leukemic transformation in patients with primary myelofibrosis. Cancer. 2008;112(12):2726-32. google scholar
  • 29. Huang J, Tefferi A. Erythropoiesis stimulating agents have limited therapeutic activity in transfusion-dependent patients with primary myelofibrosis regardless of serum erythropoietin level. Eur J Haematol. 2009 Aug;83(2):154-5. doi: 10.1111/j.1600-0609.2009.01266.x. Epub 2009 Apr 10. google scholar
  • 30.James C, Ugo V, Le Couédic JP, Staerk J, Delhommeau F, Lacout C, Garçon L, Raslova H, Berger R, Bennaceur-Griscelli A, Villeval JL, Constantinescu SN, Casadevall N, Vainchenker W. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144-8. google scholar
  • 31.Jones LC, Tefferi A, Vuong PT, Desmond JC, Hofmann WK, Koeffler HP. Detection of aberrant gene expression in CD34+ hematopoietic stem cells from patients with agnogenic myeloid metaplasia using oligonucleotide microarrays. Stem Cells. 2005;23(5):631-7. google scholar
  • 32.Jowitt SN, Burke DK, Leggat HM, Lewis PS, Cryer RJ. Pleural effusion secondary to extramedullary haemopoiesis in a patient with idiopathic myelofibrosis responding to pleurodesis and hydroxyurea. Clin Lab Haematol. 1997;19(4):283-5. google scholar
  • 33. Kahn A, Bernard JF, Cottreau D, Marie J, Boivin P. Gd(--) Abrami: a deficient G-6PD variant with hemizygous expression in blood cells of a woman with primary myelofibrosis. Humangenetik. 1975;30(1):41-6. google scholar
  • 34. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352(17):1779-90. google scholar
  • 35. Kreft A, Weiss M, Wiese B, Choritz H, Buhr T, Büsche G, Georgii A. Chronic idiopathic myelofibrosis: prognostic impact of myelofibrosis and clinical parameters on event-free survival in 122 patients who presented in prefibrotic and fibrotic stages. A retrospective study identifying subgroups of different prognoses by using the RECPAM method. Ann Hematol. 2003;82(10):605-11. google scholar
  • 36. Kreipe H, Jaquet K, Felgner J, Radzun HJ, Parwaresch MR. Clonal granulocytes and bone marrow cells in the cellular phase of agnogenic myeloid metaplasia. Blood. 1991;78(7):1814-7. google scholar
  • 37. Lasho TL, Jimma T, Finke CM, Patnaik M, Hanson CA, Ketterling RP, Pardanani A, Tefferi A. SRSF2 mutations in primary myelofibrosis: significant clustering with IDH mutations and independent association with inferior overall and leukemia-free survival. Blood. 2012;120(20):4168-71. google scholar
  • 38. Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D'Andrea A, Fröhling S, Döhner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ, Gilliland DG. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7(4):387-97. google scholar
  • 39. Ligumski M, Polliack A, Benbassat J. Myeloid metaplasia of the central nervous system in patients with myelofibrosis and agnogenic myeloid metaplasia. Report of 3 cases and review of the literature. Am J Med Sci. 1978;275(1):99-103. google scholar
  • 40. Loewy G, Mathew A, Distenfeld A. Skin manifestation of agnogenic myeloid metaplasia. Am J Hematol. 1994;45(2):167-70. google scholar
  • 41. Martínez-Trillos A, Gaya A, Maffioli M, ArellanoRodrigo E, Calvo X, Díaz-Beyá M, Cervantes F. Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients. Ann Hematol. 2010;89(12):1233-7. google scholar
  • 42. Mascarenhas J, Lu M, Li T, Petersen B, Hochman T, Najfeld V, Goldberg JD, Hoffman R. A phase I study of panobinostat (LBH589) in patients with primary myelofibrosis (PMF) and postpolycythaemia vera/essential thrombocythaemia myelofibrosis (post-PV/ET MF). Br J Haematol. 2013;161(1):68-75. google scholar
  • 43. Mesa RA, Li CY, Ketterling RP, Schroeder GS, Knudson RA, Tefferi A. Leukemic transformation in myelofibrosis with myeloid metaplasia: a singleinstitution experience with 91 cases. Blood. 2005;105(3):973-7. google scholar
  • 44. Mesa RA, Nagorney DS, Schwager S, Allred J, Tefferi A. Palliative goals, patient selection, and perioperative platelet management: outcomes and lessons from 3 decades of splenectomy for myelofibrosis with myeloid metaplasia at the Mayo Clinic. Cancer 2006;107:361–370. google scholar
  • 45. Mishchenko E, Tefferi A. Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shunt. Eur J Haematol. 2010;85(3):192-9. google scholar
  • 46. Pardanani A, Gotlib JR, Jamieson C, Cortes JE, Talpaz M, Stone RM, Silverman MH, Gilliland DG, Shorr J, Tefferi A. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol. 2011;29(7):789-96. google scholar
  • 47. Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, Guglielmelli P, Pungolino E, Caramella M, Maffioli M, Pascutto C, Lazzarino M, Cazzola M, Tefferi A. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood. 2010;115(9):1703-8. google scholar
  • 48.Rambaldi A, Dellacasa CM, Finazzi G, Carobbio A, Ferrari ML, Guglielmelli P, Gattoni E, Salmoiraghi S, Finazzi MC, Di Tollo S, D'Urzo C, Vannucchi AM, Barosi G, Barbui T. A pilot study of the Histone-Deacetylase inhibitor Givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms. Br J Haematol. 2010;150(4):446-55. google scholar
  • 49.Rege-Cambrin G, Speleman F, Kerim S, Scaravaglio P, Carozzi F, Dal Cin P, Michaux JL, Offner F, Saglio G, Van den Berghe H. Extra translocation +der(1q9p) is a prognostic indicator in myeloproliferative disorders. Leukemia. 1991;5(12):1059-63. google scholar
  • 50.Reilly JT, Snowden JA, Spearing RL, Fitzgerald PM, Jones N, Watmore A, Potter A. Cytogenetic abnormalities and their prognostic significance in idiopathic myelofibrosis: a study of 106 cases. Br J Haematol. 1997;98(1):96-102. google scholar
  • 51. Reilly JT, Wilson G, Barnett D, Watmore A, Potter A. Karyotypic and ras gene mutational analysis in idiopathic myelofibrosis. Br J Haematol. 1994;88(3):575-81. google scholar
  • 52.Rupoli S, Da Lio L, Sisti S, Campanati G, Salvi A, Brianzoni MF, D'Amico S, Cinciripini A, Leoni P. Primary myelofibrosis: a detailed statistical analysis of the clinicopathological variables influencing survival. Ann Hematol. 1994;68(4):205-12. google scholar
  • 53. Santos FP, Kantarjian HM, Jain N, Manshouri T, Thomas DA, Garcia-Manero G, Kennedy D, Estrov Z, Cortes J, Verstovsek S. Phase 2 study of CEP701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Blood. 2010;115(6):1131-6.. google scholar
  • 54. Taksin AL, Couedic JP, Dusanter-Fourt I, Massé A, Giraudier S, Katz A, Wendling F, Vainchenker W, Casadevall N, Debili N. Autonomous megakaryocyte growth in essential thrombocythemia and idiopathic myelofibrosis is not related to a c-mpl mutation or to an autocrine stimulation by Mpl-L. Blood. 1999;93(1):125-39. google scholar
  • 55. Tefferi A. Primary myelofibrosis: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol. 2013;88(2):141-50. google scholar
  • 56. Tefferi A, Cortes J, Verstovsek S, Mesa RA, Thomas D, Lasho TL, Hogan WJ, Litzow MR, Allred JB, Jones D, Byrne C, Zeldis JB, Ketterling RP, McClure RF, Giles F, Kantarjian HM. Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood. 2006;108(4):1158-64. Epub 2006 Apr 11. google scholar
  • 57. Tefferi A, Elliot MA, Yoon SY, Li CY, Mesa RA, Call TG, Dispenzieri A. Clinical and bone marrow effects of interferon alfa therapy in myelofibrosis with myeloid metaplasia. Blood. 2001 Mar 15;97(6):1896. google scholar
  • 58. Tefferi A, Lasho TL, Huang J, Finke C, Mesa RA, Li CY, Wu W, Hanson CA, Pardanani A. Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival. Leukemia. 2008;22(4):756-61. google scholar
  • 59. Tefferi A, Lasho TL, Mesa RA, Pardanani A, Ketterling RP, Hanson CA. Lenalidomide therapy in del(5)(q31)-associated myelofibrosis: cytogenetic and JAK2V617F molecular remissions. Leukemia. 2007;21(8):1827-8. Epub 2007 Apr 26. google scholar
  • 60. Tefferi A, Litzow MR, Pardanani A. Long-term outcome of treatment with ruxolitinib in myelofibrosis. N Engl J Med. 2011;365(15):1455-7. google scholar
  • 61. Tefferi A, Mesa RA, Schroeder G, Hanson CA, Li CY, Dewald GW. Cytogenetic findings and their clinical relevance in myelofibrosis with myeloid metaplasia. Br J Haematol. 2001 Jun;113(3):763-71. google scholar
  • 62. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and pointof-care diagnostic algorithms. Leukemia. 2008; 22(1):14-22. Comment in: Leukemia. 2008;22(11):2118-9. google scholar
  • 63. Tefferi A, Verstovsek S, Barosi G, Passamonti F, Roboz GJ, Gisslinger H, Paquette RL, Cervantes F, Rivera CE, Deeg HJ, Thiele J, Kvasnicka HM, Vardiman JW, Zhang Y, Bekele BN, Mesa RA, Gale RP, Kantarjian HM. Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol. 2009;27(27):4563-9. google scholar
  • 64. homas DA, Giles FJ, Albitar M, Cortes JE, Verstovsek S, Faderl S, O'Brien SM, Garcia-Manero G, Keating MJ, Pierce S, Zeldis J, Kantarjian HM. Thalidomide therapy for myelofibrosis with myeloid metaplasia. Cancer. 2006;106(9):1974-84. google scholar
  • 65. Tsukamoto N, Morita K, Maehara T, Okamoto K, Sakai H, Karasawa M, Naruse T, Omine M. Clonality in chronic myeloproliferative disorders defined by X-chromosome linked probes: demonstration of heterogeneity in lineage involvement. Br J Haematol. 1994;86(2):253-8. google scholar
  • 66. Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, Estrov Z, Fridman JS, Bradley EC, Erickson-Viitanen S, Vaddi K, Levy R, Tefferi A. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010;363(12):1117- 27. google scholar
  • 67. Wang JC, Chen C. P16 gene deletions and point mutations in patients with agnogenic myeloid metaplasia (AMM). Leuk Res. 1999;23(7):631-5. google scholar
  • 68. Wanless IR, Peterson P, Das A, Boitnott JK, Moore GW, Bernier V. Hepatic vascular disease and portal hypertension in polycythemia vera and agnogenic myeloid metaplasia: a clinicopathological study of 145 patients examined at autopsy. Hepatology. 1990;12(5):1166-74. google scholar
  • 69. Williams ME, Innes DJ, Hutchison WT, Hess CE. Extramedullary hematopoiesis. A cause of severe generalized lymphadenopathy in agnogenic myeloid metaplasia. Arch Intern Med. 1985;145(7):1308-9. google scholar
  • 70. Yotsumoto M, Ishida F, Ito T, Ueno M, Kitano K, Kiyosawa K. Idiopathic myelofibrosis with refractory massive ascites. Intern Med. 2003;42(6):525-8. google scholar
  • 71. Zojer N, Meran JG, Vesely M, Grüner H, Ackermann J, Dellinger C, Zimmer-Roth I, Heinz R, Drach J, Ludwig H. Trisomy 13 is associated with poor prognosis in idiopathic myelofibrosis with myeloid metaplasia. Leuk Lymphoma. 1999;35(3- 4):415-21. google scholar

Atıflar

Biçimlendirilmiş bir atıfı kopyalayıp yapıştırın veya seçtiğiniz biçimde dışa aktarmak için seçeneklerden birini kullanın


DIŞA AKTAR



APA

Yönal Hindilerden, İ., & Sargın, F.D. (2014). PRİMER MİYELOFİBROZİS: PATOGENEZ, TEŞHİS VE TEDAVİDE GÜNCEL BİLGİLER. İstanbul Tıp Fakültesi Dergisi, 77(4), 67-77. https://doi.org/https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77


AMA

Yönal Hindilerden İ, Sargın F D. PRİMER MİYELOFİBROZİS: PATOGENEZ, TEŞHİS VE TEDAVİDE GÜNCEL BİLGİLER. İstanbul Tıp Fakültesi Dergisi. 2014;77(4):67-77. https://doi.org/https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77


ABNT

Yönal Hindilerden, İ.; Sargın, F.D. PRİMER MİYELOFİBROZİS: PATOGENEZ, TEŞHİS VE TEDAVİDE GÜNCEL BİLGİLER. İstanbul Tıp Fakültesi Dergisi, [Publisher Location], v. 77, n. 4, p. 67-77, 2014.


Chicago: Author-Date Style

Yönal Hindilerden, İpek, and Fatma Deniz Sargın. 2014. “PRİMER MİYELOFİBROZİS: PATOGENEZ, TEŞHİS VE TEDAVİDE GÜNCEL BİLGİLER.” İstanbul Tıp Fakültesi Dergisi 77, no. 4: 67-77. https://doi.org/https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77


Chicago: Humanities Style

Yönal Hindilerden, İpek, and Fatma Deniz Sargın. “PRİMER MİYELOFİBROZİS: PATOGENEZ, TEŞHİS VE TEDAVİDE GÜNCEL BİLGİLER.” İstanbul Tıp Fakültesi Dergisi 77, no. 4 (May. 2025): 67-77. https://doi.org/https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77


Harvard: Australian Style

Yönal Hindilerden, İ & Sargın, FD 2014, 'PRİMER MİYELOFİBROZİS: PATOGENEZ, TEŞHİS VE TEDAVİDE GÜNCEL BİLGİLER', İstanbul Tıp Fakültesi Dergisi, vol. 77, no. 4, pp. 67-77, viewed 25 May. 2025, https://doi.org/https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77


Harvard: Author-Date Style

Yönal Hindilerden, İ. and Sargın, F.D. (2014) ‘PRİMER MİYELOFİBROZİS: PATOGENEZ, TEŞHİS VE TEDAVİDE GÜNCEL BİLGİLER’, İstanbul Tıp Fakültesi Dergisi, 77(4), pp. 67-77. https://doi.org/https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77 (25 May. 2025).


MLA

Yönal Hindilerden, İpek, and Fatma Deniz Sargın. “PRİMER MİYELOFİBROZİS: PATOGENEZ, TEŞHİS VE TEDAVİDE GÜNCEL BİLGİLER.” İstanbul Tıp Fakültesi Dergisi, vol. 77, no. 4, 2014, pp. 67-77. [Database Container], https://doi.org/https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77


Vancouver

Yönal Hindilerden İ, Sargın FD. PRİMER MİYELOFİBROZİS: PATOGENEZ, TEŞHİS VE TEDAVİDE GÜNCEL BİLGİLER. İstanbul Tıp Fakültesi Dergisi [Internet]. 25 May. 2025 [cited 25 May. 2025];77(4):67-77. Available from: https://doi.org/https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77 doi: https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77


ISNAD

Yönal Hindilerden, İpek - Sargın, FatmaDeniz. “PRİMER MİYELOFİBROZİS: PATOGENEZ, TEŞHİS VE TEDAVİDE GÜNCEL BİLGİLER”. İstanbul Tıp Fakültesi Dergisi 77/4 (May. 2025): 67-77. https://doi.org/https://doi.org/10.18017/iuitfd.13056441.2015.77/4.67-77



ZAMAN ÇİZELGESİ



PAYLAŞ



İstanbul Üniversitesi Yayınları, uluslararası yayıncılık standartları ve etiğine uygun olarak, yüksek kalitede bilimsel dergi ve kitapların yayınlanmasıyla giderek artan bilimsel bilginin yayılmasına katkıda bulunmayı amaçlamaktadır. İstanbul Üniversitesi Yayınları açık erişimli, ticari olmayan, bilimsel yayıncılığı takip etmektedir.