联合检测中危组成人急性髓系白血病患者MDR1与BAALC基因mRNA表达水平及其临床意义

Abstract

急性髓系白血病(Acute myeloid leukemia, AML)是高度异质性疾病，存在多种具有不同功能的临床意义的基因或分子学异常。我们已经证明了MDR1、BAALC基因均为AML重要的独立预后指标。但是联合检测这两个指标对于中危组AML预后的意义尚未进行阐述。方法：使用实时定量PCR方法检测105例初治成人中危组AML的骨髓标本中MDR1和BAALC基因mRNA水平。将AML患者根据两个基因表达水平分别分为高表达组和低表达组，并统计分析两组病例中临床预后间差异。结果：105例中危组AML中首次诱导化疗后CR率为79.0% (83/105)，复发率为38.6% (32/83)。根据MDR1和BAALC基因表达情况，将105例患者分为4组。MDR1基因和BAALC基因均高表达组、MDR1基因高表达而BAALC基因低表达组、MDR1基因低表达而BAALC基因高表达组、MDR1基因和BAALC基因均低表达组。前三组间病人的一般情况及预后资料之间无统计学差异，因此将后组合并为一个组，即高MDR1和/或高BAALC基因表达组。低MDR1/低BAALC患者的CR率(91.4% vs 72.9%, P = 0.028)和OS (79.7% vs 25.3%, P = 0.000)明显高于高MDR1和/或高BAALC基因高表达组，而复发率明显低于MDR1和/或BAALC基因高表达组(15.6% vs 52.9%, P = 0.001)。结论：联合检测MDR1和BAALC基因表达有助于提高成人中危组AML的分层级预后判断，低MDR1/低BAALC的AML患者预后较好。 Objective: Acute myeloid leukemia (AML) is a heterogeneous disease, in terms of genetic/mole- cular abnormalities resulting into marked differences in outcome. We had demonstrated that MDR1, BAALC expression were of prognostic significance and high MDR1 expression correlated with a high BAALC expression in intermediate-risk AML in the prophase study. We founded that MDR1 and BAALC expression together would better identify the patient’s risk profile. Methods: Pretreatment bone marrow samples from 105 adult intermediate risk group AML (IR-AML) patients were analyzed for MDR1 and BAALC mRNA expression by real-time reverse transcriptase polymerase chain reaction. Patients were divided into different groups according to MDR1 and BAALC levels and were compared for clinical outcome. Results: 83 cases of 105 IR-AML patients got CR after the first block with a CR rate being 79.0%. However, 32 cases of the CR patients with IR-AML relapsed with the relapsed rate being 38.6%. On the basis of MDR1 and BAALC expression status, we identified four different subgroups: low MDR1/low BAALC (N = 35), low MDR1/high BAALC (N = 17), high MDR1/low BAALC (N = 17), and high MDR1/high BAALC (N = 36). Patients with high expression of MDR1 and/or BAALC were characterized by an inferior outcome with no significant differences between the three groups; thus, these patients were considered a single group. Patients with low MDR1/low BAALC had a superior CR rate (91.4% vs 72.9%, P = 0.028), OS (79.7% vs 25.3%, P = 0.000) and lower relapse rate 15.6% vs 52.9%, P = 0.001) than high MDR1 and/or high BAALC expression in IR-AML. Conclusion: The combined assessment of BAALC and MDR1 expression can improve treatment stratification in adult IR-AML. Low expression of both MDR1 and BAALC identifies IR-AML patients with a favorable long-term outcome.