title: Gene expression ratio as a predictive determinant of nelarabine chemosensitivity in T-lymphoblastic leukemia/lymphoma.
abstract: Nelarabine has been used for the treatment of T-cell malignancies including T-acute lymphoblastic leukemia (T-ALL)/T-lymphoblastic lymphoma. However, the mechanisms that underlie the susceptibility or resistance to nelarabine have not been fully elucidated. The aim of this study was to determine the significance of nelarabine transport and metabolism in the context of nelarabine cytotoxicity.
  
  
  
  The expression profiles of six genes in the nelarabine pathway were analyzed in blast cells from six patients with T-ALL as well as in three T-ALL cell lines. In vitro cytotoxicity (LC50of 9-β-d-arabinofuranosylguanine [ara-G]) was evaluated.
  
  
  
  The mRNA expression of ENT1, DCK, CDA, NT5C2, RRM1, and RRM2 in patients showed inter-individual variability and was not correlated with the LC50of ara-G. However, the ratio of (ENT1 × DCK)/(CDA × RRM1) expression was significantly correlated with LC50(r = -0.831, P = 0.0405).
  
  
  
  Chemosensitivity to nelarabine is influenced by the balance of the expression of these four genes, and the ratio of their expression predicts the response of T-cell malignancies to nelarabine.
authors: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.|Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
authors: Pornpun
authors: P
authors: Sripornsawan
authors: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Yasuhiro
authors: Y
authors: Okamoto
authors: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Takuro
authors: T
authors: Nishikawa
authors: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Yuichi
authors: Y
authors: Kodama
authors: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Yuni
authors: Y
authors: Yamaki
authors: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Koichiro
authors: K
authors: Kurauchi
authors: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Takayuki
authors: T
authors: Tanabe
authors: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Shunsuke
authors: S
authors: Nakagawa
authors: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Yuichi
authors: Y
authors: Shinkoda
authors: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Naoko
authors: N
authors: Imuta
authors: Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Yoshifumi
authors: Y
authors: Kawano
mesh_terms: D001087:Arabinonucleosides / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012262:Ribonucleoside Diphosphate Reductase; D059467:Transcriptome; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D001087:Arabinonucleosides; D014408:Biomarkers, Tumor; C470477:CDAN1 protein, human; D033721:Equilibrative Nucleoside Transporter 1; D006023:Glycoproteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C438649:SLC29A1 protein, human; D025521:Tumor Suppressor Proteins; C104457:nelarabine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase
keywords: Chemosensitivity; T-acute lymphoblastic leukemia; gene expression; gene expression ratio; nelarabine