异常的可变剪接（AS）参与了白血病的发生。该研究探讨了全球AS模式的改变对341例在国立台湾大学医院新诊断的急性髓系白血病（AML）患者的临床影响，并使用癌症基因组图谱 (The Cancer Genome Atlas，TCGA) 验证了这一影响。在研究正常的脐带血CD34+ /CD38-细胞时，我们发现白血病细胞的全局剪接模式明显不同。TP53突变的AML表现出了特别高程度的基因组范围内剪接异常。全局剪接模式的异常是一种独立的不利预后因素，影响接受标准强化化疗的AML患者的总体生存。将全局剪接模式整合到2022年欧洲白血病网络风险分层法中，可以将AML患者分成四组，这四组在我们的实验和TCGA队列中具有不同的预后。我们进一步确定了四个在这些队列中具有预后意义的AS变化基因。此外，这些与生存有关的AS事件参与了几个重要的细胞过程，可能与强化化疗的反应差有关。总之，我们的研究证实了AML患者全局剪接模式差异的临床和生物学意义。需要更大的前瞻性队列的进一步研究以确认这些发现。 本文章受版权保护。版权所有，翻译仅供参考。

Aberrant alternative splicing (AS) is involved in leukemogenesis. This study explored the clinical impact of alterations in global AS patterns in 341 patients with acute myeloid leukemia (AML) newly diagnosed at the National Taiwan University Hospital and validated it using The Cancer Genome Atlas (TCGA) cohort. While studying normal cord blood CD34+ /CD38- cells, we found that AML cells exhibited significantly different global splicing patterns. AML with mutated TP53 had a particularly high degree of genome-wide aberrations in the splicing patterns. Aberrance in the global splicing pattern was an independent unfavorable prognostic factor affecting the overall survival of patients with AML receiving standard intensive chemotherapy. The integration of global splicing patterns into the 2022 European LeukemiaNet risk classification could stratify AML patients into four groups with distinct prognoses in both our experimental and TCGA cohorts. We further identified four genes with AS alterations that harbored prognostic significance in both of these cohorts. Moreover, these survival-associated AS events are involved in several important cellular processes that might be associated with poor response to intensive chemotherapy. In summary, our study demonstrated the clinical and biological implications of differential global splicing patterns in AML patients. Further studies with larger prospective cohorts are required to confirm these findings. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.