Evaluation of the Effect of NQO1 C609T (rs1800566) Gene Variations in Philadelphia-negative Myeloproliferative Neoplasms in Turkish Population

Teker A. B. A., ADAY A., Dermenci H., Hindilerden I. Y., YILMAZ AYDOĞAN H., ÖZTÜRK O., ...Daha Fazla

ISTANBUL MEDICAL JOURNAL, cilt.21, sa.1, ss.7-12, 2020 (ESCI) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 21 Sayı: 1
  • Basım Tarihi: 2020
  • Doi Numarası: 10.4274/imj.galenos.2019.83704
  • Dergi Adı: ISTANBUL MEDICAL JOURNAL
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.7-12
  • Anahtar Kelimeler: Myeloproliferative neoplasm, MPN, JAK2 V617F mutation, NQO1 C609T gene polymorphism, ACUTE LYMPHOBLASTIC-LEUKEMIA, NAD(P)H-QUINONE OXIDOREDUCTASE-1, PRIMARY MYELOFIBROSIS, C609T POLYMORPHISM, POLYCYTHEMIA-VERA, INCREASED RISK, NQO1 C609T, SUSCEPTIBILITY, BENZENE, JAK2
  • İstanbul Üniversitesi Adresli: Evet

Özet

Introduction: Philadelphia-negative myeloproliferative neoplasm (MPN) is a hematopoietic stem cell disorder consisting of essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) associated with myeloid cell proliferation without differentiation and maturation defects. It is characterized by hypercellular bone marrow and an increase in one or more cell lines in the peripheral blood. In the hematopoietic stem cell, Janus kinase 2 (JAK2), which is a cytoplasmic tyrosine kinase, remains constantly phosphorylated (active) as a result of the V617F somatic mutation in the pseudokinase region. Even if the phosphorylated JAK2 does not receive a stimulus, it performs signal transmission and causes continuous gene expression. This explains the excessive increase in one or more blood cell lines. NAD(P)H quinone oxidoreductase-1 (NQO1) is a phase 1 enzyme that prevents the formation of reactive and toxic semiquinone metabolites by reducing two electrons in one step. The C609T polymorphism of the NQO1 gene leads to loss of enzyme activity due to the enzyme becoming unstable. While enzyme activity is not observed in individuals with both mutant alleles, moderate activity is observed in heterozygous individuals. Studies have reported a relationship between NQO1 C609T polymorphism and various cancer types. In our study, it was aimed to investigate the possible relationship between NQO1 C609T polymorphism and MPN development.