Institute of Hematology and Transfusion Medicine, Indiry Gandhi Str. 14, 02-776, Warsaw, Poland,
Ann Hematol. 2014 Apr;93(4):577-93. doi: 10.1007/s00277-013-1898-7. Epub 2013 Sep 13.
Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) and mixed-lineage leukemia gene-partial tandem duplication (MLL-PTD) are aberrations associated with leukemia which indicate unsatisfactory prognosis. Downstream regulatory targets of FLT3-ITD and MLL-PTD are not well defined. We have analyzed the expression of MDR-1, multidrug resistant protein-1 (MRP-1), breast cancer resistance protein (BCRP), and lung resistance protein (LRP) messenger RNA (mRNA) in relation to the mutational status of FLT3-ITD and MLL-PTD in 185 acute myeloid leukemia (AML) adult patients. The real-time quantitative polymerase chain reaction method was performed to assess the expression of the MDR-1, MRP-1, BCRP, and LRP mRNA, and the results were presented as coefficients calculated using an intermediate method according to Pfaffl's rule. Significantly higher expressions of MDR-1 mRNA were found in patients who did not harbor FLT3-ITD (0.20 vs. 0.05; p = 0.0001) and MRP-1 mRNA in patients with this mutation (0.96 vs. 0.70; p = 0.002) and of BCRP mRNA in patients with MLL-PTD (0.61 vs. 0.38; p = 0.03). In univariate analysis, the high expression of MDR-1 mRNA (≥0.1317) negatively influenced the outcome of induction therapy (p = 0.05), whereas the high expression of BCRP mRNA (≥1.1487) was associated with a high relapse rate (RR) (p = 0.013). We found that the high expression of MDR-1 (≥0.1317), MRP-1 (≥0.8409), and BCRP mRNA (≥1.1487) significantly influenced disease-free survival (DFS; p = 0.059, 0.032, and 0.009, respectively) and overall survival (0.048, 0.014, and 0.059, respectively). Moreover, a high expression of BCRP mRNA (≥1.1487) proved to be an independent prognostic factor for RR (p = 0.01) and DFS (p = 0.002) in multivariate analysis. The significant correlation between the expression of MDR-1, MRP-1, and BCRP mRNA and FLT3-ITD or MLL-PTD in AML patients requires further investigation.
Fms 样酪氨酸激酶 3 内部串联重复（FLT3-ITD）和混合谱系白血病基因部分串联重复（MLL-PTD）是与白血病相关的异常，表明预后不佳。FLT3-ITD 和 MLL-PTD 的下游调节靶点尚未明确。我们分析了 185 例急性髓系白血病（AML）成年患者中 FLT3-ITD 和 MLL-PTD 突变状态与多药耐药基因 1（MDR-1）、多药耐药相关蛋白 1（MRP-1）、乳腺癌耐药蛋白（BCRP）和肺耐药蛋白（LRP）信使 RNA（mRNA）表达之间的关系。采用实时定量聚合酶链反应方法评估 MDR-1、MRP-1、BCRP 和 LRP mRNA 的表达，并根据 Pfaffl 规则的中间方法计算系数表示结果。未携带 FLT3-ITD 的患者 MDR-1 mRNA 的表达显著升高（0.20 比 0.05；p=0.0001），携带该突变的患者 MRP-1 mRNA（0.96 比 0.70；p=0.002）和携带 MLL-PTD 的患者 BCRP mRNA（0.61 比 0.38；p=0.03）的表达更高。单因素分析显示，MDR-1 mRNA 高表达（≥0.1317）对诱导治疗的结果有负面影响（p=0.05），而 BCRP mRNA 高表达（≥1.1487）与高复发率（RR）相关（p=0.013）。我们发现，MDR-1（≥0.1317）、MRP-1（≥0.8409）和 BCRP mRNA（≥1.1487）的高表达显著影响无病生存（DFS；p=0.059、0.032 和 0.009）和总生存（0.048、0.014 和 0.059）。此外，BCRP mRNA 高表达（≥1.1487）在多因素分析中被证明是 RR（p=0.01）和 DFS（p=0.002）的独立预后因素。在 AML 患者中，MDR-1、MRP-1 和 BCRP mRNA 的表达与 FLT3-ITD 或 MLL-PTD 之间的显著相关性需要进一步研究。
