急性早幼粒细胞白血病PML/RARα融合基因研究及其临床意义

A study on the clinical significance of PML-RARα fusion gene in patients with promyelocytic leukemia

目的 研究急性早幼粒细胞白血病 (APL)PML/RARα融合基因的亚型、变化以及与临床疗效、预后的关系。方法 采用筑巢式逆转录酶 聚合酶链反应 (RT PCR)技术 ,检测初治APL患者PML/RARα融合基因的RNA异构体 ,监测完全缓解 (CR)APL患者微小残留病 (MRD)。结果 4 9例初治组的APL患者PML/RARα融合基因亚型 ,S型为 4 0 .8% ,L型为 5 9.2 % ;L型的复发率及早期病死率分别为 13 .8%、10 .3 % ,显著低于S型的 4 5 .0 %和 4 0 0 %。L型较S型预后较好。分别采用三氧化二砷 (AS2 O3)、全反式维甲酸 (ATRA)及柔红霉素 +阿糖胞苷 (DA)为诱导治疗 ,达CR后PML/RARα融合基因的阳性率分别为 89.5 % ,90 .9%和 5 0 .0 % ;前两组分别显著高于DA组 (P <0 .0 5 )。CR后的APL患者强烈巩固化疗 ,而使PML/RARα阳性率随缓解期的延长而逐渐降低。同时监测 15例APL患者CR后的MRL ,PML/RARα阳性患者临床复发 ,而阴性多可长期生存。结论 PML/RARα融合基因的监测对APL的确诊、疗效评估及预测预后具有重要的临床意义。

Objectives To study the conversion of PML RARα fusion gene in patients with acute promyelocytic leukemia (APL) and the relation between the expression of fusion gene and clinical prognosis. Methods By means of nested reverse transcriptase polymerase chain reaction (RT PCR) , we detected the expression patterns of PML RARα fusion gene and studied the minimal residual disease(MRD) of APL. Results Type L of PML RARα fusion gene was positive in 59.2% of the 49 untreated APL patients, while type S was positive in 40 8%. The relapse rate and early mortality was 13.8% and 10.3% respectively in type L group being significantly lower than those in the type S group. The patients with type L had better prognosis. Induction regimen of all trans retinoic acid, arsenic trioxide and DA (daunorubicin+cytarabine) was used respectively to threat the patients with APL. After remission PML RARα fusion gene was positive in 89.5%, 90.9% and 50.0% respectively. After achieving complete remission, the positive rate of PML RARα fusion gene gradually decreased. Monitoring of MRD in postremission APL by RT PCR showed that patients with positive expression would be likely to have relapse, while those with negative expression might be longer. Conclusions The detection of RT PCR PML RARα fusion gene plays an important role in the clinical diagnosis, evaluation of prognosis and prediction of relapse in APL.