Children's Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, PR China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, PR China.
Nat Commun. 2022 Jun 27;13(1):3679. doi: 10.1038/s41467-022-31489-9.
Activating FLT3 mutations are the most common mutations in acute myeloid leukemia (AML), but the optimal threshold of FLT3/ITD allelic ratio (AR) among pediatric AML patients remains controversial. Here, we present the outcome and prognostic significance of FLT3/ITD AR analysis among pediatric patients with AML from the TARGET dataset. Applying fitting curve models and threshold effect analysis using the restrictive cubic spline function following Cox proportional hazards models identifies the cut-off value of 0.5 on FLT3/ITD AR. Moreover, we observe that high FLT3/ITD AR patients have an inferior outcome when compared to low AR patients. Our study also demonstrates that stem cell transplantation may improve the outcome in pediatric AML patients with high FLT3/ITD AR and may be further improved when combined with additional therapies such as Gemtuzumab Ozogamicin. These findings underline the importance of individualized treatment of pediatric AML.
FLT3 基因突变是急性髓系白血病（AML）中最常见的突变，但儿科 AML 患者中 FLT3/ITD 等位基因比例（AR）的最佳阈值仍存在争议。在这里，我们展示了 TARGET 数据集中小儿 AML 患者中 FLT3/ITD AR 分析的结果和预后意义。通过 Cox 比例风险模型后的限制性立方样条函数拟合曲线模型和阈值效应分析，确定 FLT3/ITD AR 的截断值为 0.5。此外，我们观察到高 FLT3/ITD AR 患者的预后明显不如低 AR 患者。我们的研究还表明，干细胞移植可以改善高 FLT3/ITD AR 儿科 AML 患者的预后，当与吉妥珠单抗奥佐米星等其他治疗方法联合使用时，可能会进一步改善。这些发现强调了对儿科 AML 进行个体化治疗的重要性。
