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Esansiyel Trombositemi Hastalarında JAK2-V617F Mutasyonu ile Klinik Sonlanım Belirteçleri Arasındaki Ilişki

Yıl 2019, Cilt: 41 Sayı: 1, 81 - 86, 01.01.2019
https://doi.org/10.20515/otd.416890

Öz



Esansiyel
Trombositoz (ET)’da
JAK2-
V617F mutasyonunun klinik önemi halen belirsizdir. Bununla beraber, lökositoz,
anemi, trombositoz, ileri yaş, splenomegali varlığı tromboz, hemoraji, yaşam
süresinde kısalma gibi olumsuz klinik sonlanımlarla ilişkilendirilmektedir. Bu
nedenle, çalışmamızda JAK2 mutasyonu ile olumsuz klinik sonlanım gösteren
parametrelerin ilişkisini araştırdık. Böylece JAK2 mutasyonunun bu
parametrelerle ilişkisinin saptanması prognostik önemi konusunda bilgi
verebilir.
Bu retrospektif, kesitsel çalışma
2013 yılında Ankara Numune Eğitim Araştırma Hastanesi’nin Hematoloji kliniği
arşivlerinde dosya taraması ile gerçekleştirilmiştir. ET tanısı alan ve
dosyasında JAK2 mutasyon analizi sonucu bulunan tüm vakalar çalışmaya dahil
edilmiştir. ET tanısı Dünya Sağlık Örgütü (DSÖ) ET için Tanı Kriterleri’ne göre
konulmuştur. Demografik bilgiler, tam kan sayımı, abdominal ultrason sonuçları,
JAK2 mutasyon analizi sonuçları 84 hasta için toplanmıştır. JAK2 mutasyonu ile
yaş, cinsiyet, hemoglobin düzeyi, lökosit sayısı, trombosit sayısı ve
splenomegali varlığı arasındaki ilişki uygun istatistiksel yöntemler
kullanılarak araştırılmıştır.Hastaların yüzde 54,7’sinde JAK2 mutasyonu pozitif
saptanmıştır. JAK2 pozitifliği olan hastaların lökosit sayıları daha yüksek
(p <0.001), hemoglobin
düzeyleri daha yüksek (p = 0.014) saptanmıştır ve splenomegali bu hastalarda
daha sık görülmüştür (p <0.001). JAK2 mutasyonu ile yaş, cinsiyet, trombosit
sayıları ve anemi durumu arasında istatistiksel anlamlı ilişki saptanmamıştır.
JAK2 mutasyonu trombotik risk faktörü olarak bilinen lökositoz ve splenomegali
ile ilişkili bulunmuştur. Bu durum JAK2 mutasyonunun prognostik değeri
olabileceğini göstermektedir. 

Kaynakça

  • Tefferi A. The Philadelphia chromosome negative chronic myeloproliferative disorders: a practical overview. Mayo Clin Proc. 1998;73(12):1177-84.
  • Schafer AI. Thrombocytosis. N Engl J Med. 2004;350(12):1211-9.
  • Ma X, Vanasse G, Cartmel B, Wang Y, Selinger HA. Prevalence of polycythemia vera and essential thrombocythemia. Am J Hematol. 2008;83(5):359-62.
  • Bellucci S, Janvier M, Tobelem G, Flandrin G, Charpak Y, Berger R, et al. Essential thrombocythemias. Clinical evolutionary and biological data. Cancer. 1986;58(11):2440-7.
  • van Genderen PJ, Mulder PG, Waleboer M, van de Moesdijk D, Michiels JJ. Prevention and treatment of thrombotic complications in essential thrombocythaemia: efficacy and safety of aspirin. Br J Haematol. 1997;97(1):179-84.
  • Schafer AI. Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia. Blood. 2006;107(11):4214-22.
  • Gale RE, Allen AJ, Nash MJ, Linch DC. Long-term serial analysis of X-chromosome inactivation patterns and JAK2 V617F mutant levels in patients with essential thrombocythemia show that minor mutant-positive clones can remain stable for many years. Blood. 2007;109(3):1241-3.
  • Beer PA, Erber WN, Campbell PJ, Green AR. How I treat essential thrombocythemia. Blood. 2011;117(5):1472-82.
  • Wong RS, Cheng CK, Chan NP, Cheng SH, Wong WS, Lau KM, et al. JAK2 V617F mutation is associated with increased risk of thrombosis in Chinese patients with essential thrombocythaemia. Br J Haematol. 2008;141(6):902-4.
  • Wolanskyj AP, Lasho TL, Schwager SM, McClure RF, Wadleigh M, Lee SJ, et al. JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol. 2005;131(2):208-13.
  • Ruggeri M, Finazzi G, Tosetto A, Riva S, Rodeghiero F, Barbui T. No treatment for low-risk thrombocythaemia: results from a prospective study. Br J Haematol. 1998;103(3):772-7.
  • Fenaux P, Simon M, Caulier MT, Lai JL, Goudemand J, Bauters F. Clinical course of essential thrombocythemia in 147 cases. Cancer. 1990;66(3):549-56.
  • Tefferi A, Fonseca R, Pereira DL, Hoagland HC. A long-term retrospective study of young women with essential thrombocythemia. Mayo Clin Proc. 2001;76(1):22-8.
  • Gangat N, Wolanskyj AP, McClure RF, Li CY, Schwager S, Wu W, et al. Risk stratification for survival and leukemic transformation in essential thrombocythemia: a single institutional study of 605 patients. Leukemia. 2007;21(2):270-6.
  • Wolanskyj AP, Schwager SM, McClure RF, Larson DR, Tefferi A. Essential thrombocythemia beyond the first decade: life expectancy, long-term complication rates, and prognostic factors. Mayo Clin Proc. 2006;81(2):159-66.
  • Carobbio A, Finazzi G, Antonioli E, Vannucchi AM, Barosi G, Ruggeri M, et al. Hydroxyurea in essential thrombocythemia: rate and clinical relevance of responses by European LeukemiaNet criteria. Blood. 2010;116(7):1051-5.
  • Carobbio A, Antonioli E, Guglielmelli P, Vannucchi AM, Delaini F, Guerini V, et al. Leukocytosis and risk stratification assessment in essential thrombocythemia. J Clin Oncol. 2008;26(16):2732-6.
  • Barbui T, Carobbio A, Rambaldi A, Finazzi G. Perspectives on thrombosis in essential thrombocythemia and polycythemia vera: is leukocytosis a causative factor? Blood. 2009;114(4):759-63.
  • Teofili L, Giona F, Torti L, Cenci T, Ricerca BM, Rumi C, et al. Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis. Haematologica. 2010;95(1):65-70.
  • Kittur J, Knudson RA, Lasho TL, Finke CM, Gangat N, Wolanskyj AP, et al. Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer. 2007;109(11):2279-84.
  • Speletas M, Katodritou E, Daiou C, Mandala E, Papadakis E, Kioumi A, et al. Correlations of JAK2-V617F mutation with clinical and laboratory findings in patients with myeloproliferative disorders. Leuk Res. 2007;31(8):1053-62.
  • Campbell PJ, Scott LM, Buck G, Wheatley K, East CL, Marsden JT, et al. Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. Lancet. 2005;366(9501):1945-53.
  • Cheung B, Radia D, Pantelidis P, Yadegarfar G, Harrison C. The presence of the JAK2 V617F mutation is associated with a higher haemoglobin and increased risk of thrombosis in essential thrombocythaemia. Br J Haematol. 2006;132(2):244-5.
  • Landolfi R, Di Gennaro L, Barbui T, De Stefano V, Finazzi G, Marfisi R, et al. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood. 2007;109(6):2446-52.
  • Potaczek DP, Jankowska EA, Wypasek E, Undas A. Iron deficiency: a novel risk factor of recurrence in patients after unprovoked venous thromboembolism. Pol Arch Med Wewn. 2016;126(3):159-65.
  • Lieu CH, Wu HS, Hon YC, Tsai WH, Yang CF, Wang CC, et al. Prevalence of the JAK2-V617F mutation in Taiwanese patients with chronic myeloproliferative disorders. Intern Med J. 2008;38(6):422-6.
  • Palandri F, Ottaviani E, Salmi F, Catani L, Polverelli N, Fiacchini M, et al. JAK2 V617F mutation in essential thrombocythemia: correlation with clinical characteristics, response to therapy and long-term outcome in a cohort of 275 patients. Leuk Lymphoma. 2009;50(2):247-53.
  • Vannucchi AM, Antonioli E, Guglielmelli P, Longo G, Pancrazzi A, Ponziani V, et al. Prospective identification of high-risk polycythemia vera patients based on JAK2(V617F) allele burden. Leukemia. 2007;21(9):1952-9.

The Relationship Between the JAK2-V617F Mutation Status and Predictors of Clinical Outcomes in Patients with Essential Thrombocythemia

Yıl 2019, Cilt: 41 Sayı: 1, 81 - 86, 01.01.2019
https://doi.org/10.20515/otd.416890

Öz

The prognostic value of JAK2 - V617F mutation
remains unclear in essential thrombocythemia (ET). However, leukocytosis,
anemia, thrombocytosis, advanced age, and splenomegaly are all associated with
poor clinical outcomes, such as thrombosis, hemorrhage, and short life
expectancy. JAK2 mutation may be related to these parameters and may
establish prognostic value in this regard. Therefore, we investigated the
relationship between JAK2 mutation
and these predictors of poor prognosis.
This
retrospective, cross-sectional study is
conducted in
archives of a Hematology Clinic in an Education Hospital at
2013. All patients who have been
diagnosed with ET and have JAK2 mutation
analysis results, are included to the study. Diagnosis of ET was made according
to the World Health Organization (WHO) Diagnostic Criteria for ET. Demographic
characteristics, complete blood counts, abdominal ultrasounds and JAK2 mutation analyses are collected
from patient files for 84 patients. The relationship between JAK2 mutation and age, sex, hemoglobin,
leukocyte, thrombocyte counts, and splenomegaly is analyzed by using
appropriate statistical analysis. In
total,
54.7% of patients with ET tested positive for the JAK2 mutation. Patients with JAK2 mutation had higher leukocyte
levels (
p < 0.001), higher hemoglobin
levels (
p = 0.014), and splenomegaly (p < 0.001). There was no
relationship between JAK2 mutation
and age, sex, thrombocyte counts or anemia. The JAK2
mutation is related to leukocytosis and splenomegaly, which are known to be
thrombotic risk factors. Therefore, JAK2
mutation may have a prognostic value and warrants further research with
clinical outcomes.

Kaynakça

  • Tefferi A. The Philadelphia chromosome negative chronic myeloproliferative disorders: a practical overview. Mayo Clin Proc. 1998;73(12):1177-84.
  • Schafer AI. Thrombocytosis. N Engl J Med. 2004;350(12):1211-9.
  • Ma X, Vanasse G, Cartmel B, Wang Y, Selinger HA. Prevalence of polycythemia vera and essential thrombocythemia. Am J Hematol. 2008;83(5):359-62.
  • Bellucci S, Janvier M, Tobelem G, Flandrin G, Charpak Y, Berger R, et al. Essential thrombocythemias. Clinical evolutionary and biological data. Cancer. 1986;58(11):2440-7.
  • van Genderen PJ, Mulder PG, Waleboer M, van de Moesdijk D, Michiels JJ. Prevention and treatment of thrombotic complications in essential thrombocythaemia: efficacy and safety of aspirin. Br J Haematol. 1997;97(1):179-84.
  • Schafer AI. Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia. Blood. 2006;107(11):4214-22.
  • Gale RE, Allen AJ, Nash MJ, Linch DC. Long-term serial analysis of X-chromosome inactivation patterns and JAK2 V617F mutant levels in patients with essential thrombocythemia show that minor mutant-positive clones can remain stable for many years. Blood. 2007;109(3):1241-3.
  • Beer PA, Erber WN, Campbell PJ, Green AR. How I treat essential thrombocythemia. Blood. 2011;117(5):1472-82.
  • Wong RS, Cheng CK, Chan NP, Cheng SH, Wong WS, Lau KM, et al. JAK2 V617F mutation is associated with increased risk of thrombosis in Chinese patients with essential thrombocythaemia. Br J Haematol. 2008;141(6):902-4.
  • Wolanskyj AP, Lasho TL, Schwager SM, McClure RF, Wadleigh M, Lee SJ, et al. JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol. 2005;131(2):208-13.
  • Ruggeri M, Finazzi G, Tosetto A, Riva S, Rodeghiero F, Barbui T. No treatment for low-risk thrombocythaemia: results from a prospective study. Br J Haematol. 1998;103(3):772-7.
  • Fenaux P, Simon M, Caulier MT, Lai JL, Goudemand J, Bauters F. Clinical course of essential thrombocythemia in 147 cases. Cancer. 1990;66(3):549-56.
  • Tefferi A, Fonseca R, Pereira DL, Hoagland HC. A long-term retrospective study of young women with essential thrombocythemia. Mayo Clin Proc. 2001;76(1):22-8.
  • Gangat N, Wolanskyj AP, McClure RF, Li CY, Schwager S, Wu W, et al. Risk stratification for survival and leukemic transformation in essential thrombocythemia: a single institutional study of 605 patients. Leukemia. 2007;21(2):270-6.
  • Wolanskyj AP, Schwager SM, McClure RF, Larson DR, Tefferi A. Essential thrombocythemia beyond the first decade: life expectancy, long-term complication rates, and prognostic factors. Mayo Clin Proc. 2006;81(2):159-66.
  • Carobbio A, Finazzi G, Antonioli E, Vannucchi AM, Barosi G, Ruggeri M, et al. Hydroxyurea in essential thrombocythemia: rate and clinical relevance of responses by European LeukemiaNet criteria. Blood. 2010;116(7):1051-5.
  • Carobbio A, Antonioli E, Guglielmelli P, Vannucchi AM, Delaini F, Guerini V, et al. Leukocytosis and risk stratification assessment in essential thrombocythemia. J Clin Oncol. 2008;26(16):2732-6.
  • Barbui T, Carobbio A, Rambaldi A, Finazzi G. Perspectives on thrombosis in essential thrombocythemia and polycythemia vera: is leukocytosis a causative factor? Blood. 2009;114(4):759-63.
  • Teofili L, Giona F, Torti L, Cenci T, Ricerca BM, Rumi C, et al. Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis. Haematologica. 2010;95(1):65-70.
  • Kittur J, Knudson RA, Lasho TL, Finke CM, Gangat N, Wolanskyj AP, et al. Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer. 2007;109(11):2279-84.
  • Speletas M, Katodritou E, Daiou C, Mandala E, Papadakis E, Kioumi A, et al. Correlations of JAK2-V617F mutation with clinical and laboratory findings in patients with myeloproliferative disorders. Leuk Res. 2007;31(8):1053-62.
  • Campbell PJ, Scott LM, Buck G, Wheatley K, East CL, Marsden JT, et al. Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. Lancet. 2005;366(9501):1945-53.
  • Cheung B, Radia D, Pantelidis P, Yadegarfar G, Harrison C. The presence of the JAK2 V617F mutation is associated with a higher haemoglobin and increased risk of thrombosis in essential thrombocythaemia. Br J Haematol. 2006;132(2):244-5.
  • Landolfi R, Di Gennaro L, Barbui T, De Stefano V, Finazzi G, Marfisi R, et al. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood. 2007;109(6):2446-52.
  • Potaczek DP, Jankowska EA, Wypasek E, Undas A. Iron deficiency: a novel risk factor of recurrence in patients after unprovoked venous thromboembolism. Pol Arch Med Wewn. 2016;126(3):159-65.
  • Lieu CH, Wu HS, Hon YC, Tsai WH, Yang CF, Wang CC, et al. Prevalence of the JAK2-V617F mutation in Taiwanese patients with chronic myeloproliferative disorders. Intern Med J. 2008;38(6):422-6.
  • Palandri F, Ottaviani E, Salmi F, Catani L, Polverelli N, Fiacchini M, et al. JAK2 V617F mutation in essential thrombocythemia: correlation with clinical characteristics, response to therapy and long-term outcome in a cohort of 275 patients. Leuk Lymphoma. 2009;50(2):247-53.
  • Vannucchi AM, Antonioli E, Guglielmelli P, Longo G, Pancrazzi A, Ponziani V, et al. Prospective identification of high-risk polycythemia vera patients based on JAK2(V617F) allele burden. Leukemia. 2007;21(9):1952-9.
Toplam 28 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm ORİJİNAL MAKALELER / ORIGINAL ARTICLES
Yazarlar

Mehmet Erdem Alagüney

Funda Ceran Bu kişi benim 0000-0003-3173-7614

Mesude Falay Bu kişi benim 0000-0001-7846-3476

Simten Dağdaş Bu kişi benim 0000-0003-0901-2043

Gülsüm Özet Bu kişi benim 0000-0003-2658-5978

Yayımlanma Tarihi 1 Ocak 2019
Yayımlandığı Sayı Yıl 2019 Cilt: 41 Sayı: 1

Kaynak Göster

Vancouver Alagüney ME, Ceran F, Falay M, Dağdaş S, Özet G. The Relationship Between the JAK2-V617F Mutation Status and Predictors of Clinical Outcomes in Patients with Essential Thrombocythemia. Osmangazi Tıp Dergisi. 2019;41(1):81-6.


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