Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer, Praça Cruz Vermelha 23, 6º andar, Centro, Rio de Janeiro, RJ CEP 20230-130, Brazil.
J Cancer Res Clin Oncol. 2012 Jun;138(6):959-69. doi: 10.1007/s00432-012-1170-x. Epub 2012 Feb 23.
Polymorphisms in the ABCB1 gene may influence P-glycoprotein (Pgp) expression and/or activity. Because the population in Brazil is markedly heterogeneous, we analyzed the relationship between ABCB1 polymorphisms and Pgp expression/activity in Brazilian acute myeloid leukemia (AML) patients.
Acute myeloid leukemia samples from 109 patients were studied. ABCB1 gene variants rs1128503 (C1236T) and rs1045643 (C3435T) were analyzed by PCR-RFLP assay. Pgp expression and Pgp activity were analyzed by flow cytometry.
There was a similar distribution of Pgp expression and activity on polymorphisms C1236T, C1236C, and T1236T for exon 12, and C3435T, C3435C, and T3435T for exon 26. An exception was observed in the lowest ratio of mean fluorescence intensity (MFI) median for Pgp expression in the TT genotype for both studied exons, and its correspondence to a low MFI median for Pgp activity. Pgp expression did not show impact on the response to remission induction therapy, but the MFI median of Pgp expression in the remission failure group was higher than that of the complete remission (CR) group of patients (p = 0.04). Overall survival (OS) was significantly influenced by CR (p = 0.0001). Better 5-year OS and 5-year event-free survival rates (p = 0.04 and p = 0.007, respectively) were achieved in patients presenting the genetic variant CC in exon 12 followed by those presenting the variant CT in exon 26 (p = 0.001).
Polymorphisms in the ABCB1 gene and the levels of Pgp expression could be useful to identify prognostic in AML patients.
ABCB1 基因多态性可能影响 P-糖蛋白（Pgp）的表达和/或活性。由于巴西人口明显具有异质性，我们分析了 ABCB1 多态性与巴西急性髓细胞白血病（AML）患者 Pgp 表达/活性之间的关系。
研究了 109 例急性髓细胞白血病患者的样本。通过 PCR-RFLP 分析检测 ABCB1 基因变体 rs1128503（C1236T）和 rs1045643（C3435T）。通过流式细胞术分析 Pgp 表达和 Pgp 活性。
在exon12 的 C1236T、C1236C 和 T1236T 以及 exon26 的 C3435T、C3435C 和 T3435T 多态性中，Pgp 表达和活性的分布相似。在两个研究外显子的 TT 基因型中，Pgp 表达的平均荧光强度（MFI）中位数的最低比值观察到一个例外，并且与 Pgp 活性的低 MFI 中位数相对应。Pgp 表达对缓解诱导治疗的反应没有影响，但缓解失败组的 Pgp 表达 MFI 中位数高于完全缓解（CR）组患者（p=0.04）。总生存（OS）受到 CR 的显著影响（p=0.0001）。在外显子 12 中存在 CC 遗传变异的患者随后在外显子 26 中存在 CT 变异的患者的 5 年 OS 和 5 年无事件生存（EFS）率更好（p=0.04 和 p=0.007，分别）。
ABCB1 基因多态性和 Pgp 表达水平可用于识别 AML 患者的预后。
