Department of Hematopathology and Laboratory Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
University of South Florida, Internal Medicine, Tampa, FL, USA.
Leuk Res. 2021 Dec;111:106733. doi: 10.1016/j.leukres.2021.106733. Epub 2021 Oct 21.
Recent studies demonstrated that MYC epigenetically regulates AML cell survival and differentiation by suppressing IDH1/2-TET2-5hmC signaling and that MYC overexpression is associated with poor survival outcomes in multiple AML patient cohorts. However, the oncogenic roles of MYC in MDS remain to be explored. A total of 41 patients with de novo MDS were retrospectively identified using the Total Cancer Care database at the Moffitt Cancer Center. A total of 61 % of patients had low MYC expression and 39 % of patients had high MYC expression defined as MYC reactivity by immunohistochemical staining in ≥5% of bone marrow (BM) cells at the time of MDS diagnosis. The median MDS-to-AML progression free survival (PFS) was significantly shorter in the high MYC group (median PFS 9.3 vs. 17.7 months, HR = 2.328, p = 0.013). Further, overall survival (OS) was also shorter in the high MYC patients (median OS 19.7 vs. 51.7 months, HR = 2.299, p = 0.053). Multivariate analyses demonstrated that high MYC expression is an independent poor prognostic factor for the MDS-to-AML progression (HR = 2.275, p = 0.046). Our observations indicate that MYC may play a crucial role in MDS transformation to AML and the underlying mechanisms of MYC-driven MDS clonal expansion and leukemic transformation require further investigation.
最近的研究表明，MYC 通过抑制 IDH1/2-TET2-5hmC 信号来表观遗传调控 AML 细胞的存活和分化，并且 MYC 的过表达与多个 AML 患者队列的不良生存结果相关。然而，MYC 在 MDS 中的致癌作用仍有待探索。使用 Moffitt 癌症中心的 Total Cancer Care 数据库，回顾性地确定了 41 例初发 MDS 患者。共有 61%的患者 MYC 表达低，39%的患者 MYC 表达高，定义为在 MDS 诊断时骨髓（BM）细胞中 MYC 反应性免疫组化染色≥5%。高 MYC 组的 MDS 向 AML 无进展生存期（PFS）明显缩短（中位 PFS 9.3 与 17.7 个月，HR=2.328，p=0.013）。此外，高 MYC 患者的总生存期（OS）也较短（中位 OS 19.7 与 51.7 个月，HR=2.299，p=0.053）。多变量分析表明，高 MYC 表达是 MDS 向 AML 进展的独立不良预后因素（HR=2.275，p=0.046）。我们的观察表明，MYC 可能在 MDS 向 AML 的转化中发挥关键作用，需要进一步研究 MYC 驱动的 MDS 克隆扩增和白血病转化的潜在机制。
