Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Leukemia. 2021 Mar;35(3):691-700. doi: 10.1038/s41375-020-0920-z. Epub 2020 Jun 19.
While germline and somatic mutations in the gene PTPN11, encoding a phosphatase which regulates the RAS signaling pathway, are well characterized in children with Noonan syndrome and juvenile myelomonocytic leukemia, less is known about their clinical impact in adults with acute myeloid leukemia (AML). To elucidate the effect of PTPN11 mutations (PTPN11) on clinical outcomes, we screened adult patients with AML treated at our institution using targeted next-generation sequencing. Among 1406 consecutive patients, 112 (8%) had PTPN11. These mutations were more commonly associated with the acute myelomonocytic/monocytic leukemia subtype than was wild-type PTPN11, while none were detected in patients with core-binding factor AML. They co-occurred more commonly with NPM1 mutations and FLT3 internal tandem duplications and less commonly with mutations in IDH2 and a complex karyotype. Compared with the wild-type allele, PTPN11 was associated with lower complete response rates (54% vs 40%; P = 0.04), and shorter overall survival (median 13.6 vs 8.4 months; P = 0.008). In a multivariate analysis, PTPN11 independently increased the risk of death, with a hazard ratio of 1.69 (95% CI, 1.25-2.29; P = 0.0007). In summary, mutations in PTPN11 have a characteristic phenotype in adults with AML and are associated with an adverse prognosis.
虽然编码一种调节 RAS 信号通路的磷酸酶的基因 PTPN11 的种系和体细胞突变在 Noonan 综合征和青少年骨髓单核细胞白血病患儿中得到了很好的描述，但在急性髓细胞白血病 (AML) 成人中，其临床影响知之甚少。为了阐明 PTPN11 突变 (PTPN11) 对临床结果的影响，我们使用靶向下一代测序筛选了在我们机构治疗的 AML 成年患者。在 1406 例连续患者中，有 112 例 (8%) 存在 PTPN11。与野生型 PTPN11 相比，这些突变更常见于急性髓单核细胞/单核细胞白血病亚型，而在核心结合因子 AML 患者中未检测到。它们与 NPM1 突变和 FLT3 内部串联重复更常见共发生，与 IDH2 突变和复杂核型较少共发生。与野生型等位基因相比，PTPN11 与较低的完全缓解率相关 (54% 对 40%；P=0.04)，总生存期较短 (中位 13.6 对 8.4 个月；P=0.008)。在多变量分析中，PTPN11 独立增加了死亡风险，危险比为 1.69 (95% CI，1.25-2.29；P=0.0007)。总之，PTPN11 突变在 AML 成人中具有特征性表型，并与不良预后相关。
