Objective: Bone marrow fibrosis is the second most common complication that causes morbidity and mortality in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs). The aim of this study was to investigate the association between JAK2V617F mutation and bone marrow fibrosis at diagnosis in patients with MPNs.
Material and Methods: In total, 149 patients with MPNs were retrospectively evaluated to determine if there was an association between the histological grade of bone marrow fibrosis and JAK2V617F mutation.
Results: In all, 67.7% of the patients carried the mutated JA1K2 gene. The presence of JAK2V617F mutation was not associated with the occurrence of bone marrow fibrosis (P = 0.55) or its grade at diagnosis (P = 0.65).
Conclusion: Molecular mechanisms or genetic defects other than JAK2V617F may underlie the occurrence of bone marrow fibrosis in patients with MPNs.
Key Words: JAK2V617F, Myeloproliferative disease, Bone marrow fibrosis
Amac: Kemik iligi fibrozu, Philadelphia negatif miyeloproliferatif neoplazili (MPN) hastalarda morbidite ve mortaliteye yol acan ikinci en sik komplikasyondur. Bu calismanin amaci MPN'li hastalarda tani aninda kemik iliginde gorulen fibroz ile JAK2V617F mutasyonu arasindaki iliskinin arastirilmasidir.
Gerec ve Yontemler: Calismaya retrospektif olarak dahil edilen 149 MPN tanili hasta JAK2V617F mutasyonu ile kemik iligindeki fibroz arasindaki iliski acisindan degerlendirilmistir.
Bulgular: calismaya alinanhastalarin %67.7'sindeJAK2V617F genmutasyonunarastlandt.AncakJAK2V617Fmutasyonu ile kemik iligindeki fibroz varligi ve derecesi arasinda iliski saptanmadi (sirasiyla, P = 0.55 ve P = 0.65).
Sonuc: MPN'de gorulen kemik iligi fibrozunun altinda JAK2V617F mutasyonu disinda bazi molekuler mekanizma veya genetik bozukluklarin yattigi sonucuna varilmistir.
Anahtar Sozcukler: JAK2V617F, Miyeloproliferatif hastalik, Kemik iligi fibrozu
Polycythemia vera (PV), primary myelofibrosis (PMF), and essential thrombocythemia (ET) are the 3 classical Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs) that are characterized by clonal proliferation of multipotent hematopoietic progenitor cells. New discoveries concerning the molecular pathogenesis of MPNs have changed the nature of their classification and diagnosis. (1) Janus kinase 2V617F (JAK2V617F) point mutation is a recently identified acquired genetic defect that is present in 95% and 50% of patients with PV and ET/PM", respectively. (2-4) The mutation encodes an inducible tyrosine kinase of the intracellular signaling pathway that promotes myeloid proliferation and differentiation.
Bone marrow fibrosis occurs either as a primary disease (PMF) or as a late complication of PV and ET. Fibrosis contributes to morbidity and mortality in patients with MPNs together with additional risk factors. (5), (6) Patients usually suffer from fatigue, malaise, weight loss, bone pain, and abdominal distension. The severity of symptoms is associated with the extent of anemia and splenomegaly. Unfortunately, treatment has been palliative and mostly disappointing until recently, consisting mainly of transfusion and other modalities that reduce the size of the spleen. Discovery of JAK2V617F mutation and current progress in the molecule targeted treatment technologies lead to the development of JAK2 inhibitors which seem to yield promising results in selected groups of patients with myelofibrosis and created a certain enthusiasm. But further evidence from randomized studies should be awaited before drawing firm conclusions on the role of JAK2 inhibitors in the management of MPN associated bone marrow fibrosis....
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