title: Relationship between SLCO1B3 and ABCA3 polymorphisms and imatinib response in chronic myeloid leukemia patients.
abstract: BACKGROUND
  Genetic variations in membrane transporters may contribute to imatinib mesylate (IM) resistance in chronic myeloid leukemia (CML). Objective To investigate the relationship between SLCO1B3, SLCO1A2, and ABCA3 polymorphisms and IM response in CML patients.
  
  
  METHODS
  Patients in chronic phase CML (N = 118) were studied. All patients were treated with a standard dose of IM (400 mg/day) and classified into one of the two groups according to their responses. Major molecular response (MMR) and complete molecular response (CMR) were evaluated. Criteria for response failure were established according to European LeukemiaNet (2009). Analysis of the SLCO1B3 c.334T > G (rs4149117) and c.699G > A (rs7311358), SLCO1A2 c.516A > C (rs11568563) and c.-62-361G > A (rs3764043), and ABCA3 c.1755C > G (rs323043) and c.4548-191C > A (rs150929) polymorphisms was carried out by real-time polymerase chain reaction.
  
  
  RESULTS
  SLCO1A2 and ABCA3 polymorphisms have similar frequencies between responders and non-responders. SLCO1B3 699GG and 344TT genotypes were more frequent in the responder group (63.8%) than in the non-responder group (44.7%, P = 0.042). Furthermore, carriers of 699GA/AA and 334TG/GG genotypes presented a higher probability of not responding to the standard dose of IM (odds ratio: 2.17; 95% confidence interval: 1.02-4.64, P = 0.04). Poor CMR for ABCA3 4548-91C > A was observed in patients with the CC/CA genotype when compared to AA carriers in the responder group (P = 0.014).
  
  
  CONCLUSIONS
  SLCO1B3 699GG and 344TT genotypes are associated with non-response to IM, while ABCA3 4548-91 CC/CA genotypes are related to poor CMR in CML patients treated with standard-dose imatinib.
authors: Luciene Terezina
authors: LT
authors: de Lima
authors: Carolina Tosin
authors: CT
authors: Bueno
authors: Douglas
authors: D
authors: Vivona
authors: Rosario Domiguez Crespo
authors: RD
authors: Hirata
authors: Mario Hiroyuki
authors: MH
authors: Hirata
authors: Vania Tiestsche de Moraes
authors: VT
authors: Hungria
authors: Carlos Sérgio
authors: CS
authors: Chiattone
authors: Maria Aparecida
authors: MA
authors: Zanichelli
authors: Maria de Lourdes Lopes Ferrari
authors: Mde L
authors: Chauffaille
authors: Elvira Maria
authors: EM
authors: Guerra-Shinohara
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D016896:Treatment Outcome
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D047428:Protein Kinase Inhibitors; C512988:SLCO1A2 protein, human; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
keywords: ABCA3; Chronic myeloid leukemia; Imatinib; Membrane transporters; Pharmacogenetics; Resistance; SLCO1B3