Koller E, Karlic H, Krieger O, Mistrik M, Michlmayr G, Gadner H, Lutz D, Heinz R, Pittermann E
3rd Medical Department, Hanusch Hospital, Vienna, Austria.
Ann Hematol. 1995 Feb;70(2):75-8. doi: 10.1007/BF01834383.
The PML/RAR alpha fusion RNA can be detected in acute promyelocytic leukemia (APL), cytogenetically characterized by the translocation t(15;17). Our study included ten newly diagnosed patients with APL who were investigated during the course of their diseases using reverse transcription polymerase chain reaction (RT-PCR). At diagnosis, aberrant fragments with a size heterogeneity due to alternative spliced products were detected in all patients, we observed breakpoints within bcr3 (short type) in two patients and bcr1 and 2 breakpoints (long type) in eight patients. Treatment consisted of all-trans retinoic acid (ATRA) in all patients; six patients received simultaneous cytostatic therapy during remission induction. At the time of complete hematological remission (CR), only two patients showed a negative RT-PCR result; eight of the ten patients were still PCR positive when nested primers were used. Subsequently, eight patients received consolidation chemotherapy and became PCR negative. Seven of eight patients are in continuous complete remission (median remission duration: 21 months, range: 11+ -26+ months). One patient of the chemotherapy group became PCR positive after 4 months in complete remission and relapsed after 6 months. The remaining two patients who were treated only with ATRA relapsed, received induction chemotherapy, and are in second and third complete remission, respectively. In conclusion. PCR negativity can be achieved only by chemotherapeutic consolidation; patients treated with ATRA alone remain PCR positive. Relapse is always preceded by a positive PCR result. Surprisingly, also patients without measurable PML/RAR alpha-mRNA in sequential analyses after cytostatic treatment became PCR positive and experienced relapse.
在急性早幼粒细胞白血病（APL）中可检测到PML/RARα融合RNA，其细胞遗传学特征为t(15;17)易位。我们的研究纳入了10例新诊断的APL患者，在其病程中采用逆转录聚合酶链反应（RT-PCR）进行调查。诊断时，所有患者均检测到由于可变剪接产物导致大小异质性的异常片段，我们观察到2例患者的断点位于bcr3（短型），8例患者的断点位于bcr1和2（长型）。所有患者均接受全反式维甲酸（ATRA）治疗；6例患者在缓解诱导期同时接受了细胞抑制治疗。在完全血液学缓解（CR）时，只有2例患者RT-PCR结果为阴性；10例患者中有8例在使用巢式引物时PCR仍为阳性。随后，8例患者接受巩固化疗并转为PCR阴性。8例患者中有7例处于持续完全缓解状态（中位缓解持续时间：21个月，范围：11 + - 26 +个月）。化疗组的1例患者在完全缓解4个月后PCR转为阳性，6个月后复发。其余仅接受ATRA治疗的2例患者复发，接受诱导化疗，分别处于第二次和第三次完全缓解状态。总之，只有通过化疗巩固才能实现PCR阴性；仅接受ATRA治疗的患者PCR仍为阳性。复发前PCR结果总是呈阳性。令人惊讶的是，在细胞抑制治疗后的连续分析中无可测量PML/RARα - mRNA的患者也转为PCR阳性并经历了复发。
