Department of Biomedicine and Prevention, University of Tor Vergata, Rome, Italy.
Neuro-Oncohematology, Santa Lucia Foundation, I.R.C.C.S., Rome, Italy.
Am J Hematol. 2019 Oct;94(10):1091-1097. doi: 10.1002/ajh.25573. Epub 2019 Jul 23.
Despite the high probability of cure of patients with acute promyelocytic leukemia (APL), mechanisms of relapse are still largely unclear. Mutational profiling at diagnosis and/or relapse may help to identify APL patients needing frequent molecular monitoring and early treatment intervention. Using an NGS approach including a 31 myeloid gene-panel, we tested BM samples of 44 APLs at the time of diagnosis, and of 31 at relapse. Mutations in PML and RARA genes were studied using a customized-NGS-RNA panel. Patients relapsing after ATRA-chemotherapy rarely had additional mutations (P = .009). In patients relapsing after ATRA/ATO, the PML gene was a preferential mutation target. We then evaluated the predictive value of mutations at APL diagnosis. A median of two mutations was detectable in 9/11 patients who later relapsed, vs one mutation in 21/33 patients who remained in CCR (P = .0032). This corresponded to a significantly lower risk of relapse in patients with one or less mutations (HR 0.046; 95% CI 0.011-0.197; P < .0001). NGS-analysis at the time of APL diagnosis may inform treatment decisions, including alternative treatments for cases with an unfavorable mutation profile.
尽管急性早幼粒细胞白血病 (APL) 患者的治愈可能性很高，但复发的机制仍很大程度上不清楚。在诊断时和/或复发时进行突变分析可能有助于确定需要频繁进行分子监测和早期治疗干预的 APL 患者。我们使用包括 31 个骨髓基因在内的 NGS 方法，检测了 44 例 APL 患者在诊断时和 31 例复发时的 BM 样本。使用定制的 NGS-RNA 面板研究了 PML 和 RARA 基因突变。接受 ATRA-化疗后复发的患者很少有额外的突变（P = 0.009）。在接受 ATRA/ATO 后复发的患者中，PML 基因是优先突变靶点。然后，我们评估了 APL 诊断时突变的预测价值。在 11 例随后复发的患者中有 9 例可检测到中位数为 2 个突变，而在 33 例持续完全缓解的患者中有 21 例患者检测到 1 个突变（P = 0.0032）。这表明突变数量少的患者（1 个或更少）复发风险显著降低（HR 0.046；95%CI 0.011-0.197；P < 0.0001）。APL 诊断时的 NGS 分析可以为治疗决策提供信息，包括对具有不利突变谱的病例提供替代治疗。
