Pediatric Hematology-Oncology Center, Zhejiang Provincial Center for Childhood Leukemia Diagnosis and Treatment, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Acornmed Biotechnology Co., Ltd, Tianjin, China.
BMC Pediatr. 2023 Feb 4;23(1):62. doi: 10.1186/s12887-023-03856-y.
The 5-year survival rate of children with acute lymphoblastic leukemia (ALL) is 85-90%, with a 10-15% rate of treatment failure. Next-generation sequencing (NGS) identified recurrent mutated genes in ALL that might alter the diagnosis, classification, prognostic stratification, treatment, and response to ALL. Few studies on gene mutations in Chinese pediatric ALL have been identified. Thus, an in-depth understanding of the biological characteristics of these patients is essential. The present study aimed to characterize the spectrum and clinical features of recurrent driver gene mutations in a single-center cohort of Chinese pediatric ALL.
We enrolled 219 patients with pediatric ALL in our single center. Targeted sequencing based on NGS was used to detect gene mutations in patients. The correlation was analyzed between gene mutation and clinical features, including patient characteristics, cytogenetics, genetic subtypes, risk stratification and treatment outcomes using χ-square test or Fisher's exact test for categorical variables.
A total of 381 gene mutations were identified in 66 different genes in 152/219 patients. PIK3R1 mutation was more common in infants (P = 0.021). KRAS and FLT3 mutations were both more enriched in patients with hyperdiploidy (both P < 0.001). NRAS, PTPN11, FLT3, and KMT2D mutations were more common in patients who did not carry the fusion genes (all P < 0.050). PTEN mutation was significantly associated with high-risk ALL patients (P = 0.011), while NOTCH1 mutation was common in middle-risk ALL patients (P = 0.039). Patients with ETV6 or PHF6 mutations were less sensitive to steroid treatment (P = 0.033, P = 0.048, respectively).
This study depicted the specific genomic landscape of Chinese pediatric ALL and revealed the relevance between mutational spectrum and clinical features of Chinese pediatric ALL, which highlights the need for molecular classification, risk stratification, and prognosis evaluation.
儿童急性淋巴细胞白血病（ALL）的 5 年生存率为 85-90%，治疗失败率为 10-15%。下一代测序（NGS）鉴定出 ALL 中反复出现的突变基因，这些基因可能改变诊断、分类、预后分层、治疗和 ALL 反应。在中国儿科 ALL 中，很少有关于基因突变的研究。因此，深入了解这些患者的生物学特征是至关重要的。本研究旨在描述中国儿科 ALL 中反复出现的驱动基因突变的谱和临床特征。
我们在单中心纳入了 219 例儿科 ALL 患者。使用基于 NGS 的靶向测序检测患者的基因突变。使用卡方检验或 Fisher 精确检验分析基因突变与临床特征之间的相关性，包括患者特征、细胞遗传学、遗传亚型、风险分层和治疗结果。
在 152/219 例患者的 66 个不同基因中发现了 381 个基因突变。PIK3R1 突变在婴儿中更为常见（P=0.021）。KRAS 和 FLT3 突变在高倍体患者中更为丰富（均 P<0.001）。NRAS、PTPN11、FLT3 和 KMT2D 突变在未携带融合基因的患者中更为常见（均 P<0.050）。PTEN 突变与高危 ALL 患者显著相关（P=0.011），而 NOTCH1 突变在中危 ALL 患者中常见（P=0.039）。携带 ETV6 或 PHF6 突变的患者对激素治疗不敏感（P=0.033，P=0.048）。
本研究描绘了中国儿科 ALL 的特定基因组图谱，揭示了突变谱与中国儿科 ALL 临床特征之间的相关性，突出了分子分类、风险分层和预后评估的必要性。
