Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave., Wuhan, 430030, People's Republic of China.
Sci Rep. 2021 Dec 21;11(1):24290. doi: 10.1038/s41598-021-03709-7.
Acute leukemia with ambiguous lineage (ALAL) is a rare and highly aggressive malignancy with limited molecular characterization and therapeutic recommendations. In this study, we retrospectively analyzed 1635 acute leukemia cases in our center from January 2012 to June 2018. The diagnose of ALAL was based on either EGIL or 2016 WHO criteria, a total of 39 patients were included. Four patients diagnosed as acute undifferentiated leukemia (AUL) by both classification systems. Among the patients underwent high-throughput sequencing, 89.5% were detected at least one mutation and the median number of gene mutation was 3 (0-8) per sample. The most frequently mutated genes were NRAS (4, 21%), CEBPA (4, 21%), JAK3 (3, 16%), RUNX1 (3, 16%). The mutations detected in mixed-phenotype acute leukemia (MPAL) enriched in genes related to genomic stability and transcriptional regulation; while AUL cases frequently mutated in genes involved in signaling pathway. The survival analysis strongly suggested that mutation burden may play important roles to predict the clinical outcomes of ALAL. In addition, the patients excluded by WHO criteria had even worse clinical outcome than those included. The association of the genetic complexity of blast cells with the clinical outcomes and rationality of the diagnostic criteria of WHO system need to be evaluated by more large-scale prospective clinical studies.
急性白血病伴不定谱系（ALAL）是一种罕见且侵袭性强的恶性肿瘤，其分子特征有限，治疗建议也有限。本研究回顾性分析了 2012 年 1 月至 2018 年 6 月在我院就诊的 1635 例急性白血病患者，根据 EGIL 或 2016 年 WHO 标准诊断为 ALAL，共纳入 39 例患者。其中 4 例患者同时符合两种分类系统的急性未分化白血病（AUL）诊断标准。在接受高通量测序的患者中，89.5%至少检测到 1 个突变，每个样本的基因突变中位数为 3（0-8）个。最常见的突变基因为 NRAS（4，21%）、CEBPA（4，21%）、JAK3（3，16%）、RUNX1（3，16%）。混合表型急性白血病（MPAL）中检测到的突变富集了与基因组稳定性和转录调控相关的基因，而 AUL 病例中经常突变的基因则涉及信号通路。生存分析强烈提示突变负荷可能对预测 ALAL 的临床结局具有重要作用。此外，不符合 WHO 标准的患者的临床结局比符合标准的患者更差。需要通过更多的大规模前瞻性临床研究来评估 blast 细胞的遗传复杂性与临床结局的关系以及 WHO 系统诊断标准的合理性。
