MDR1/ABCB1 gene polymorphisms in patients with chronic myeloid leukemia.
- Author:
Mabel LARDO
1
;
Marcelo CASTRO
;
Beatriz MOIRAGHI
;
Francisca ROJAS
;
Natalia BORDA
;
Jorge A REY
;
Alberto LAZAROWSKI
Author Information
- Publication Type:Original Article
- Keywords: CML; TKIs; ABCB1; SNPs; BCR-ABL
- MeSH: Blast Crisis; Bone Marrow; Exons; Haplotypes; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive*; Polymorphism, Single Nucleotide; Prognosis; Protein-Tyrosine Kinases; Dasatinib; Imatinib Mesylate
- From:Blood Research 2015;50(3):154-159
- CountryRepublic of Korea
- Language:English
- Abstract: 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 spectrum of drugs, including TKIs. However, the association of MDR1/ABCB1 gene polymorphisms (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-patients 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 clinical-therapeutic evolution.
