Gallagher Robert E, Yeap Beow Y, Bi Wanli, Livak Kenneth J, Beaubier Nike, Rao Sreenivas, Bloomfield Clara D, Appelbaum Frederick R, Tallman Martin S, Slack James L, Willman Cheryl L
Department of Oncology and Medicine, Montefiore Medical Center and Albert Einstein Cancer Center, Bronx, NY 10467, USA.
Blood. 2003 Apr 1;101(7):2521-8. doi: 10.1182/blood-2002-05-1357. Epub 2002 Dec 5.
The potential prognostic value of quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR [qrtPCR]) measurements of PML-RAR alpha mRNA in acute promyelocytic leukemia was retrospectively assessed before treatment and at 3 posttreatment intervals in 123 patients on intergroup protocol 0129. The primary measure was the PML-RAR alpha(GAPDH) normalized quotient (NQ), that is, PML-RAR alpha mRNA copies divided by glyceraldehyde-3'-phosphate dehydrogenase (GAPDH) mRNA copies. Only samples with more than 2.5 x 10(5) copies of the housekeeping gene GAPDH mRNA (detection sensitivity exceeding 10(4)) were considered NQ evaluable. With RNA from low-density selected cells, paired peripheral blood (PB) and bone marrow samples (n = 140) had comparable NQs (P <.001). Before treatment, high NQ was associated with short-form PML-RAR alpha (P <.001), but not with white blood cell count or clinical outcome. Following treatment, NQ was lower in all-trans retinoic acid-induced complete remission (CR) than chemotherapy-induced CR (P =.018) and at first test after consolidation chemotherapy (P =.037). After consolidation chemotherapy, patients with NQ exceeding 10(-5) had 4.1-fold increased relapse risk (P =.008); however, 73% of patients who experienced relapse had NQ lower than 10(-5). In the follow-up period (FUP), any NQ exceeding 10(-5) and 10(-6) had 17.5-fold and 7.6-fold increased relapse risk, respectively (P <.001), while no gradation of relapse risk (approximately 18%) could be identified at NQ lower than 10(-6), including NQ(-). These results indicate that qrtPCR monitoring of PML-RAR alpha NQ can identify patients at high risk of relapse and suggest that clinically practical PB NQ monitoring at more frequent FUP intervals may improve predictive accuracy for relapse or continuing CR in patients with persistent, fluctuating minimal residual disease levels.
对123例参加组间方案0129的患者，在治疗前及治疗后的3个时间点，回顾性评估急性早幼粒细胞白血病中定量实时逆转录聚合酶链反应（RT-PCR [qrtPCR]）检测PML-RARα mRNA的潜在预后价值。主要测量指标是PML-RARα（GAPDH）标准化商数（NQ），即PML-RARα mRNA拷贝数除以甘油醛-3'-磷酸脱氢酶（GAPDH）mRNA拷贝数。仅管家基因GAPDH mRNA拷贝数超过2.5×10⁵（检测灵敏度超过10⁴）的样本才被视为可评估NQ。对于来自低密度选择细胞的RNA，配对的外周血（PB）和骨髓样本（n = 140）具有可比的NQ（P <.001）。治疗前，高NQ与短形式PML-RARα相关（P <.001），但与白细胞计数或临床结局无关。治疗后，全反式维甲酸诱导的完全缓解（CR）患者的NQ低于化疗诱导的CR患者（P =.018），且在巩固化疗后的首次检测时也是如此（P =.037）。巩固化疗后，NQ超过10⁻⁵的患者复发风险增加4.1倍（P =.008）；然而，73%复发的患者NQ低于10⁻⁵。在随访期（FUP），任何超过10⁻⁵和10⁻⁶的NQ分别使复发风险增加17.5倍和7.6倍（P <.001），而在低于10⁻⁶的NQ（包括NQ(-)）时，无法确定复发风险的分级（约18%）。这些结果表明，qrtPCR监测PML-RARα NQ可识别复发高风险患者，并提示在更频繁的FUP间隔进行临床上可行的PB NQ监测可能会提高对持续、波动的微小残留病水平患者复发或持续CR的预测准确性。
