Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri.
Blood Cancer Discov. 2022 Jul 6;3(4):330-345. doi: 10.1158/2643-3230.BCD-21-0155.
Progression from myelodysplastic syndromes (MDS) to secondary acute myeloid leukemia (AML) is associated with the acquisition and expansion of subclones. Our understanding of subclone evolution during progression, including the frequency and preferred order of gene mutation acquisition, remains incomplete. Sequencing of 43 paired MDS and secondary AML samples identified at least one signaling gene mutation in 44% of MDS and 60% of secondary AML samples, often below the level of standard sequencing detection. In addition, 19% of MDS and 47% of secondary AML patients harbored more than one signaling gene mutation, almost always in separate, coexisting subclones. Signaling gene mutations demonstrated diverse patterns of clonal evolution during disease progression, including acquisition, expansion, persistence, and loss of mutations, with multiple patterns often coexisting in the same patient. Multivariate analysis revealed that MDS patients who had a signaling gene mutation had a higher risk of AML progression, potentially providing a biomarker for progression.
Subclone expansion is a hallmark of progression from MDS to secondary AML. Subclonal signaling gene mutations are common at MDS (often at low levels), show complex and convergent patterns of clonal evolution, and are associated with future progression to secondary AML. See related article by Guess et al., p. 316 (33). See related commentary by Romine and van Galen, p. 270. This article is highlighted in the In This Issue feature, p. 265.
从骨髓增生异常综合征（MDS）进展为继发性急性髓系白血病（AML）与亚克隆的获得和扩增有关。我们对进展过程中亚克隆进化的理解还不完全，包括基因突变获得的频率和优先顺序。对 43 对 MDS 和继发性 AML 样本进行测序，在 44%的 MDS 和 60%的继发性 AML 样本中至少发现了一个信号基因突变，这些突变通常低于标准测序检测水平。此外，19%的 MDS 和 47%的继发性 AML 患者存在不止一个信号基因突变，几乎总是在不同的、共存的亚克隆中。信号基因突变在疾病进展过程中表现出不同的克隆进化模式，包括突变的获得、扩增、持续存在和丢失，在同一患者中通常存在多种模式共存。多变量分析显示，有信号基因突变的 MDS 患者向 AML 进展的风险更高，这可能为进展提供了一个生物标志物。
亚克隆扩增是 MDS 向继发性 AML 进展的标志。亚克隆信号基因突变在 MDS 中很常见（通常处于低水平），表现出复杂和趋同的克隆进化模式，并与未来进展为继发性 AML 相关。见 Guess 等人的相关文章，第 316 页（33）。见 Romine 和 van Galen 的相关评论，第 270 页。本文在本期特色文章中重点介绍，第 265 页。
