title: ATP-binding casette transporter expression in acute myeloid leukemia: association with in vitro cytotoxicity and prognostic markers.
abstract: BACKGROUND
  Drug resistance and relapse are considered to be the major reasons for treatment failure in acute myeloid leukemia (AML). There is limited data on the role of ABC transporter expression on in vitro sensitivity to cytarabine (Ara-C) and daunorubicin (Dnr) in primary AML cells.
  
  
  METHODS
  RNA expression levels of 12 ABC transporters were analyzed by real-time quantitative PCR in 233 de novo adult acute myeloid leukemia patients. Based on cytarabine or Dnr IC50, the samples were categorized as sensitive, intermediate and resistant. Role of candidate ABC transporter RNA expression on in vitro cytotoxicity, treatment outcome post therapy as well as the influence of various prognostic markers on ABC transporter expression were analyzed.
  
  
  RESULTS
  Expression of ABCC3 and ABCB6 were significantly higher in Dnr-resistant samples when compared with Dnr-sensitive samples. Increased ABCC1 expression was associated with poor disease-free survival in this cohort of patients.
  
  
  CONCLUSIONS
  This comprehensive analysis suggests ABCC1, ABCC3, ABCB6 and ABCA5 as probable targets which can be modulated for improving chemotherapeutic responses.
authors.affiliation: Department of Haematology, Christian Medical College, Vellore, India.
authors.forename: Savitha
authors.initials: S
authors.lastname: Varatharajan
authors.affiliation: Department of Haematology, Christian Medical College, Vellore, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Abraham
authors.affiliation: Department of Haematology, Christian Medical College, Vellore, India.
authors.forename: Sreeja
authors.initials: S
authors.lastname: Karathedath
authors.affiliation: Department of Haematology, Christian Medical College, Vellore, India.
authors.forename: Sukanya
authors.initials: S
authors.lastname: Ganesan
authors.affiliation: Department of Haematology, Christian Medical College, Vellore, India.
authors.forename: Kavitha M
authors.initials: KM
authors.lastname: Lakshmi
authors.affiliation: Department of Haematology, Christian Medical College, Vellore, India.
authors.forename: Nancy
authors.initials: N
authors.lastname: Arthur
authors.affiliation: Cytogenetics Unit, Christian Medical College, Vellore, India.
authors.forename: Vivi M
authors.initials: VM
authors.lastname: Srivastava
authors.affiliation: Department of Haematology, Christian Medical College, Vellore, India.
authors.forename: Biju
authors.initials: B
authors.lastname: George
authors.affiliation: Department of Haematology, Christian Medical College, Vellore, India.
authors.forename: Alok
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Department of Haematology, Christian Medical College, Vellore, India.
authors.forename: Vikram
authors.initials: V
authors.lastname: Mathews
authors.affiliation: Department of Haematology, Christian Medical College, Vellore, India.
authors.forename: Poonkuzhali
authors.initials: P
authors.lastname: Balasubramanian
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: ABC transporters; acute myeloid leukemia; drug resistance; in vitro cytotoxicity