Relationship between SLCO1B(3) and ABCA(3) polymorphisms and imatinib response in chronic myeloid leukemia patients

Relationship between SLCO1B(3) and ABCA(3) polymorphisms and imatinib response in chronic myeloid leukemia patients

Author Lima, Luciene Terezina de Google Scholar
Bueno, Carolina Tosin Google Scholar
Vivona, Douglas Google Scholar
Crespo Hirata, Rosario Domiguez Google Scholar
Hirata, Mario Hiroyuki Google Scholar
Moraes Hungria, Vania Tiestsche de Google Scholar
Chiattone, Carlos Sergio Google Scholar
Zanichelli, Maria Aparecida Google Scholar
Lopes Ferrari Chauffaille, Maria de Lourdes Autor UNIFESP Google Scholar
Guerra-Shinohara, Elvira Maria Google Scholar
Institution Universidade de São Paulo (USP)
Santa Casa Misericordia São Paulo
Hosp Brigadeiro
Universidade Federal de São Paulo (UNIFESP)
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.-62361G > 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 nonresponders. 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.
Keywords Imatinib
Resistance
Chronic myeloid leukemia
Membrane transporters
ABCA3
SLCO1B3
Pharmacogenetics
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 09/54184-0
Date 2015-04-01
Published in Hematology. Leeds: Maney Publishing, v. 20, n. 3, p. 137-142, 2015.
ISSN 1024-5332 (Sherpa/Romeo, impact factor)
Publisher Maney Publishing
Extent 137-142
Origin http://dx.doi.org/10.1179/1607845414Y.0000000181
Access rights Closed access
Type Article
Web of Science ID WOS:000351679100003
URI http://repositorio.unifesp.br/handle/11600/38983

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