https://scholars.lib.ntu.edu.tw/handle/123456789/631233
標題: | Evaluation of the clinical significance of global mRNA alternative splicing in patients with acute myeloid leukemia | 作者: | YI-TSUNG YANG CHI-YUAN YAO PO-JU CHIU Kao, Chein-Jun HSIN-AN HOU CHIEN-CHIN LIN WEN-CHIEN CHOU HWEI-FANG TIEN |
關鍵字: | CLASSIFICATION; COMPLEXITY; SIGNATURES; SPLICESEQ; PROGNOSIS; EVENTS | 公開日期: | 五月-2023 | 出版社: | WILEY | 卷: | 98 | 期: | 5 | 起(迄)頁: | 784 | 來源出版物: | American journal of hematology | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/631233 | ISSN: | 0361-8609 1096-8652 |
DOI: | 10.1002/ajh.26893 |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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