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KMID : 0366220150500030154
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Korean Journal of Hematology
2015 Volume.50 No. 3 p.154 ~ p.159
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MDR1/ABCB1 gene polymorphisms in patients with chronic myeloid leukemia
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Mabel Lardo
Marcelo Castro
Beatriz Moiraghi
Francisca Rojas
Natalia Borda
Jorge A Rey
Alberto Lazarowski
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Abstract
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Background: Tyrosine kinase inhibitors (TKIs) are the recommended treatment for patients with chronic myeloid leukemia (CML). The MDR1/ABCB1 gene plays a role in resistance to a wide spec-trum of drugs, including TKIs. However, the association of MDR1/ABCB1 gene poly-morphisms (SNPs) such as C1236T, G2677T/A, and C3435T with the clinical therapeutic evolution of CML has been poorly studied. We investigated these gene polymorphisms in CML-patients treated with imatinib, nilotinib and/or dasatinib.
Methods: ABCB1-SNPs were studied in 22 CML-patients in the chronic phase (CP) and 2 CML-pa-tients in blast crisis (BC), all of whom were treated with TKIs, and compared with 25 healthy controls using nested-PCR and sequencing techniques.
Results: Seventeen different haplotypes were identified: 7 only in controls, 6 only in CML-patients, and the remaining 4 in both groups. The distribution ratios of homozygous TT-variants present on each exon between controls and CML-patients were 2.9 for exon 12, and 0.32 for the other 2 exons. Heterozygous T-variants were observed in all controls (100%) and 75% of CML-patients. Wt-haplotype (CC-GG-CC) was observed in 6 CML-patients (25%). In this wt-group, two were treated with nilotinib and reached a major molecular response. The remaining 4 cases had either a minimal or null molecular response, or developed bone marrow aplasia.
Conclusion: Our results suggest that SNPs of the MDR1/ABCB1 gene could help to characterize the prognosis and the clinical-therapeutic evolution of CML-patients treated with TKIs. Wt-haplotype could be associated with a higher risk of developing CML, and a worse clin-ical-therapeutic evolution.
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KEYWORD
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CML, TKIs, ABCB1, SNPs, BCR-ABL
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