PRAME mRNA expression in newly diagnosed acute myeloid leukemia patients and its application to monitoring minimal residual disease

目的 了解黑色素瘤优先表达的抗原(PRAME)mRNA在初诊急性髓系白血病(AML)患者中的表达,评估其在微量残留病(MRD)监测中的作用.方法 采用基于TaqMan探针的实时定量RT-PCR技术检测142例初诊AML患者(其中72例不具有特异融合基因)骨髓单个核细胞PRAMEmRNA水平,动态观察3例持续缓解及6例血液学复发患者(2例不具有特异融合基因)治疗前后共60份骨髓标本PRAME mRNA水平,以22份异基因骨髓移植供者的骨髓标本作为健康对照.随访的7例AML1-ETO(+)M2患者同时检测AML1-ETO mRNA水平.以abl作为内参基因.结果 健康对照骨髓标本均表达PRAME mRNA,表达水平最高为0.28%.全部初诊AML患者骨髓中位PRAME mRNA水平为3.97%(0.00%～714.97%).无特异融合基因的AML患者骨髓中位PRAME mRNA水平为0.60%(0.00%～408.72%).PRAME mRNA水平在AML各亚型之间差异有统计学意义(P＜0.01),AML1-ETO(+)M2患者PRAME mRNA水平高于其他亚型(P值均＜0.01),S型PML-RARa(+)急性早幼粒细胞白血病患者次之.随访的AML1-ETO(+)M2患者PRAME mRNA与AML1-ETO mRNA呈现同样的变化趋势,二者呈明显正相关(r=0.88,P＜0.01).血液学复发患者中3例复发前PRAMEmRNA水平逐步升高,分别在复发前1～4个月超过正常上限,另3例患者在血液学缓解状态时PRAME mRNA水平始终未降至正常.结论 PRAME mRNA可以用于监测AML患者MRD,其水平持续升高或始终异常预示血液学复发.To investigate the expression level of preferentially expressed antigen of melanoma (PRAME) mRNA in newly diagnosed acute myeloid leukemia (AML) patients and evaluate its usefulness for detecting minimal residual disease (MRD).PRAME mRNA levels were detected in bone marrow samples from 142 newly diagnosed AML patients (72 of them didn't express any specific fusion gene) by TaqMan based real-time quantitative PCR methods, and were serially monitored in 60 bone marrow samples from 9 follow-up patients (2 of them without specific fusion gene), including 3 in continuous complete remission, 6 in hematological relapse. Bone marrow samples from 22 bone marrow donors (NBM) were served as normal controls. Samples from 7 AML1-ETO (+) M2 patients were detected for AML1-ETO mRNA simultaneously. abl was selected as control gene, PRAME and AML1-ETO mRNA levels were expressed by their copies/abl copies in percentage.All NBM samples expressed PRAME mRNA and the upper limit was 0.28%. For all newly diagnosed AML patients, median PRAME mRNA level was 3.97% (0.00%-714.97%), 76.8% of them was higher than 0.28%, 54.9% had over 1-log increasing and 26.1% had over 2-log increasing. For patients without specific fusion gene, median PRAME mRNA level was 0.60% (0.00%-408.72%), 56.3% of them was over 0.28%, 32.4% and 11.3% had over 1-log and 2-log increasing, respectively. There was a significant difference in PRAME mRNA levels between subtypes of AML patients (P<0.01). AML1-ETO (+) M2 patients expressed the highest levels (all P<0.01), followed by acute promyelocytic leukemia patients with S type PML-RAR alpha fusion gene. PRAME and AML1-ETO mRNA levels of follow up patients displayed similar kinetic patterns, and correlated well in 43 follow up samples (r=0.88, P<0.01). PRAME mRNA levels in 3 hematological relapsed patients increased above 0.28% 1-4 months ahead relapse, and in other 3 relapsed patients the levels never decreased to normal range even in remission.PRAME mRNA could be used to monitor MRD for AML patients with higher than normal levels, and it increases over or persistently higher than normal range predicts hematological relapse.PubMed中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)07441-4452