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Relationship between SLCO1B3 and ABCA3 polymorphisms and imatinib response in chronic myeloid leukemia patients

Luciene Terezina de Lima, Carolina Tosin Bueno, Douglas Vivona

    Hematology (Amsterdam, Netherlands)
    |July 25, 2014
    PubMed
    Abstract

    Insights

    Genetic variations in SLCO1B3 and ABCA3 transporters impact imatinib mesylate response in chronic myeloid leukemia (CML). Specific SLCO1B3 genotypes correlate with non-response, while ABCA3 genotypes are linked to poor complete molecular response.

    Area of Science:

    • Pharmacogenomics
    • Hematology
    • Molecular Biology

    Background:

    • Genetic variations in membrane transporters are implicated in imatinib mesylate (IM) resistance in chronic myeloid leukemia (CML).
    • Understanding these genetic factors is crucial for optimizing CML treatment.
    • This study focuses on specific polymorphisms in SLCO1B3, SLCO1A2, and ABCA3 genes.

    Purpose of the Study:

    • To investigate the association between SLCO1B3, SLCO1A2, and ABCA3 gene polymorphisms and the response to imatinib mesylate in CML patients.
    • To identify genetic markers that predict treatment outcomes in CML.
    • To explore the role of these transporters in IM resistance.

    Main Methods:

    • A cohort of 118 chronic phase CML patients treated with standard-dose IM was analyzed.
    • Real-time polymerase chain reaction was used to genotype specific polymorphisms in SLCO1B3, SLCO1A2, and ABCA3.
    • Patients were classified based on their response to IM, including major molecular response (MMR) and complete molecular response (CMR), using European LeukemiaNet 2009 criteria.

    Main Results:

    • SLCO1A2 and ABCA3 polymorphisms showed no significant difference in frequency between responders and non-responders.
    • SLCO1B3 genotypes 699GG and 334TT were more prevalent in the responder group.
    • Carriers of SLCO1B3 699GA/AA and 334TG/GG genotypes had a higher likelihood of not responding to IM (OR: 2.17, P=0.04).
    • ABCA3 4548-91 CC/CA genotypes were associated with poor CMR compared to AA carriers in responders (P=0.014).

    Conclusions:

    • Specific SLCO1B3 genotypes (699GG and 334TT) are linked to non-response to standard-dose imatinib in CML patients.
    • Certain ABCA3 genotypes (4548-91 CC/CA) are associated with suboptimal complete molecular response.
    • These findings highlight the pharmacogenetic influence of transporter genes on CML treatment efficacy.
    Keywords:
    ABCA3Chronic myeloid leukemiaImatinibMembrane transportersPharmacogeneticsResistanceSLCO1B3

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