Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Int J Mol Sci. 2017 Jul 26;18(8):1618. doi: 10.3390/ijms18081618.
(1) Runt-related transcription factor 1 () mutations in acute myeloid leukemia (AML) are often associated with worse prognosis. We assessed co-occurring mutations, response to therapy, and clinical outcomes in patients with and without mutant (); (2) We analyzed 328 AML patients, including 177 patients younger than 65 years who received intensive chemotherapy and 151 patients >65 years who received hypomethylating agents. and co-existing mutations were identified using next-generation sequencing; (3) mutations were identified in 5.1% of younger patients and 15.9% of older patients, and were significantly associated with increasing age ( = 0.01) as well as intermediate-risk cytogenetics including normal karyotype ( = 0.02) in the elderly cohort, and with lower lactate dehydrogenase (LDH; = 0.02) and higher platelet count ( = 0.012) overall. Identified co-occurring mutations were primarily mutations in older patients and mutations in younger patients; FLT3-ITD and IDH1/2 co-mutations were also frequent. Younger AML patients treated with intensive chemotherapy experienced inferior treatment outcomes. In older patients with AML treated with hypomethylating agent (HMA) therapy, response and survival was independent of status. Older patients with prior myelodysplastic syndrome or myeloproliferative neoplasms (MDS/MPN) had particularly dismal outcome. Future studies should focus on the prognostic implications of mutations relative to other co-occurring mutations, and the potential role of hypomethylating agents for this molecularly-defined group.
(1) 急性髓系白血病（AML）中 runt 相关转录因子 1 () 突变常与预后不良相关。我们评估了伴有和不伴有突变 () 的患者的合并突变、对治疗的反应和临床结局；(2) 我们分析了 328 例 AML 患者，包括 177 例年龄<65 岁接受强化化疗的患者和 151 例年龄>65 岁接受低甲基化药物治疗的患者。使用下一代测序鉴定 和合并突变；(3) 在年轻患者中，突变发生率为 5.1%，在老年患者中为 15.9%，与年龄增加显著相关（=0.01），在老年患者中与中危细胞遗传学（包括正常核型）相关（=0.02），与乳酸脱氢酶（LDH；=0.02）降低和血小板计数（=0.012）升高相关。鉴定出的合并突变主要是老年患者中的突变和年轻患者中的突变；FLT3-ITD 和 IDH1/2 共突变也很常见。接受强化化疗的年轻 AML 患者治疗结局较差。在接受低甲基化药物（HMA）治疗的老年 AML 患者中，反应和生存与 状态无关。先前患有骨髓增生异常综合征或骨髓增殖性肿瘤（MDS/MPN）的老年 AML 患者预后尤其差。未来的研究应集中在 突变相对于其他合并突变的预后意义，以及低甲基化药物对这一分子定义人群的潜在作用。
