Department of Internal Medicine, Mayo Clinic, Jacksonville, FL.
Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
Clin Lymphoma Myeloma Leuk. 2020 May;20(5):312-315. doi: 10.1016/j.clml.2019.11.007. Epub 2019 Nov 9.
Acute myeloid leukemia (AML) in elderly patients is associated with poor outcomes and often arises from antecedent hematologic disorders (AHD), classified as secondary AML (sAML).
To validate the use of somatic mutations to determine AML ontogeny in the elderly population, we identified 178 elderly (> 70 years) patients with AML with NexGen Sequencing data. Patients were divided clinically into primary AML (pAML) or sAML based on prior history of AHD. Patients were then reclassified into 4 groups based on somatic mutations and cytogenetics as suggested by Lindsley et al: group 1 (pAML) with CBF rearrangements, 11q23/MLL, and NPM1 mutation (MT); group 2 (sAML) with SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 MT; group 3 with TP53 MT; and group 4 as not otherwise specified (NOS).
Based on clinical criteria, 95 patients were classified as pAML and 82 patients as sAML. Based on the AML ontogeny proposed, 8 patients were classified as pAML, 72 patients as sAML, 28 patients had TP53 MT, and 70 patients were classified as NOS. The median overall survival was 22.4,14, 2.8, and 11.2 months, respectively. Clinical versus molecular classification was discordant where 25% (n = 2) of patients classified as pAML by molecular signature had a history of AHD, whereas 44% (n = 32) of patients classified molecularly as sAML had no prior AHD. In the TP53 MT and NOS categories, 37% (n = 28) and 43% (n = 70) of patients had AHD, respectively.
Our data shows that molecular annotation of elderly patients with AML reclassifies a significant proportion of patients as sAML, which may have therapeutic implications.
老年患者的急性髓系白血病（AML）预后较差，且常由前驱血液系统疾病（AHD）发展而来，被归类为继发性 AML（sAML）。
为了验证使用体细胞突变来确定老年人群中 AML 的发生机制，我们从 NexGen 测序数据中确定了 178 名年龄大于 70 岁的老年 AML 患者。根据前驱 AHD 病史，临床将患者分为原发性 AML（pAML）或 sAML。然后，根据 Lindsley 等人提出的体细胞突变和细胞遗传学标准，将患者重新分为 4 组：组 1（pAML）伴有 CBF 重排、11q23/MLL 和 NPM1 突变（MT）；组 2（sAML）伴有 SRSF2、SF3B1、U2AF1、ZRSR2、ASXL1、EZH2、BCOR 或 STAG2 MT；组 3 伴有 TP53 MT；组 4 为其他未分类（NOS）。
根据临床标准，95 名患者被归类为 pAML，82 名患者被归类为 sAML。根据提出的 AML 发生机制，8 名患者被归类为 pAML，72 名患者被归类为 sAML，28 名患者存在 TP53 MT，70 名患者被归类为 NOS。中位总生存期分别为 22.4、14、2.8 和 11.2 个月。临床与分子分类不一致，25%（2 例）根据分子特征归类为 pAML 的患者有 AHD 病史，而 44%（32 例）分子上归类为 sAML 的患者没有前驱 AHD。在 TP53 MT 和 NOS 类别中，分别有 37%（28 例）和 43%（70 例）的患者有 AHD。
我们的数据表明，老年 AML 患者的分子注释将很大一部分患者重新归类为 sAML，这可能具有治疗意义。
