Strickland Stephen A, Shaver Aaron C, Byrne Michael, Daber Robert D, Ferrell P Brent, Head David R, Mohan Sanjay R, Mosse Claudio A, Moyo Tamara K, Stricker Thomas P, Vnencak-Jones Cindy, Savona Michael R, Seegmiller Adam C
Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States; Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, United States.
Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States.
Leuk Res. 2018 Feb;65:67-73. doi: 10.1016/j.leukres.2017.12.012. Epub 2018 Jan 2.
The National Comprehensive Cancer Network (NCCN) defines the following types of acute myeloid leukemia (AML) as favorable-risk: acute promyelocytic leukemia with t(15;17) (APL); AML with core-binding factor (CBF) rearrangements, including t(8;21) and inv(16) or t(16;16) without mutations in KIT (CBF-KIT); and AML with normal cytogenetics and mutations in NPM1 (NPM1); or biallelic mutations in CEBPA (CEBPA), without FLT3-ITD. Although these AMLs are categorized as favorable risk by NCCN, clinical experience suggests that there are differences in clinical outcome amongst these cytogenetically and molecularly distinct leukemias. This study compared clinical and genotypic characteristics of 60 patients with favorable-risk AML, excluding APL, and demonstrated significant differences between them. Patients with NPM1 AML were significantly older than those in the other groups. Targeted next-generation sequencing on DNA from peripheral blood or bone marrow revealed significantly more mutations in NPM1 AML than the other favorable-risk diseases, especially in genes related to DNA splicing and methylation. CEBPA AMLs exhibited more mutations in transcription-related genes. Patients with NPM1 AML and CEBPA AML show significantly reduced overall survival in comparison with CBF-KIT AML. These findings emphasize that favorable-risk AML patients have divergent outcomes and that differences in clinical and genotypic characteristics should be considered in their evaluation and management.
美国国立综合癌症网络（NCCN）将以下几种急性髓系白血病（AML）定义为低危型：伴有t(15;17)的急性早幼粒细胞白血病（APL）；伴有核心结合因子（CBF）重排的AML，包括t(8;21)以及inv(16)或t(16;16)且KIT无突变（CBF-KIT）；以及细胞遗传学正常且NPM1有突变（NPM1）的AML；或CEBPA双等位基因突变（CEBPA）且无FLT3-ITD。尽管这些AML被NCCN归类为低危型，但临床经验表明，这些细胞遗传学和分子学上不同的白血病在临床结局上存在差异。本研究比较了60例低危型AML患者（不包括APL）的临床和基因型特征，并证明了它们之间存在显著差异。NPM1 AML患者的年龄显著高于其他组。对外周血或骨髓DNA进行靶向二代测序发现，NPM1 AML中的突变显著多于其他低危型疾病，尤其是在与DNA剪接和甲基化相关的基因中。CEBPA AML在转录相关基因中表现出更多突变。与CBF-KIT AML相比，NPM1 AML和CEBPA AML患者的总生存期显著缩短。这些发现强调，低危型AML患者的结局存在差异，在对他们进行评估和管理时应考虑临床和基因型特征的差异。
