Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands; Department of Pediatric Hematology, University Medical Center Utrecht, 3584 EA Utrecht, the Netherlands.
Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, the Netherlands.
Cell Rep. 2019 Sep 10;28(11):2866-2877.e5. doi: 10.1016/j.celrep.2019.08.012.
Relapse in acute myeloid leukemia (AML) may result from variable genetic origins or convergence on common biological processes. Exploiting the specificity and sensitivity of regulatory DNA, we analyze patient samples of multiple clinical outcomes covering various AML molecular subtypes. We uncover regulatory variation among patients translating into a transcriptional signature that predicts relapse risk. In addition, we find clusters of coexpressed genes within this signature selectively link to relapse risk in distinct patient subgroups defined by molecular subtype or AML maturation. Analyzing these gene clusters and the AML subtypes separately enhances their prognostic value substantially and provides insight in the mechanisms underlying relapse risk across the distinct patient subgroups. We propose that prognostic gene expression signatures in AML are valid only within patient subgroups and do not transcend these subgroups.
急性髓系白血病 (AML) 的复发可能源于不同的遗传起源，也可能是多种生物学过程趋同的结果。我们利用调控 DNA 的特异性和敏感性，分析了涵盖多种 AML 分子亚型的多种临床结局的患者样本。我们发现了患者之间的调控变化，这些变化转化为一个转录特征，可以预测复发风险。此外，我们还发现，在这个特征中，表达相关的基因簇选择性地与不同分子亚型或 AML 成熟定义的患者亚组的复发风险相关联。单独分析这些基因簇和 AML 亚型可以大大提高其预后价值，并深入了解不同患者亚组中复发风险的潜在机制。我们提出，AML 中的预后基因表达特征仅在患者亚组内有效，不能超越这些亚组。
