Department of Pathology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Department of Pathology, Vanderbilt University, Nashville, Tennessee.
Lab Med. 2021 May 4;52(3):e53-e56. doi: 10.1093/labmed/lmaa080.
FLT3 mutations are considered a prognostic and predictive marker. Here we report on a patient with a rare FLT3 germline variant in the context of relapsed acute myeloid leukemia (AML). A female patient aged 57 years presented with AML with mutations in the IDH2, ASXL1, and DNMT3A genes. She underwent allogenic hematopoietic stem cell transplant but relapsed 2 years posttransplant. Targeted next generation sequencing identified a new missense variant in the FLT3 tyrosine kinase domain c.2440G > T (p.A814S). The treating team considered the possibility of patient eligibility for an FLT3 inhibitor. Because both somatic and germline mutations can be identified in tumor tissue with high-throughput sequencing, it becomes important to distinguish the origin of these alterations when possible-especially, in this challenging case, to define the treatment modality. Simultaneous tumor/germline sequencing allows for the identification of rare germline mutations and may help in determining their significance in the pathogenesis of disease.
FLT3 突变被认为是一种预后和预测标志物。在这里，我们报告了一例在复发急性髓系白血病（AML）背景下罕见的 FLT3 种系变异的患者。一名 57 岁女性患者患有 AML，其 IDH2、ASXL1 和 DNMT3A 基因发生突变。她接受了同种异体造血干细胞移植，但在移植后 2 年复发。靶向下一代测序在 FLT3 酪氨酸激酶结构域 c.2440G>T（p.A814S）中发现了一个新的错义变异。治疗团队考虑了患者是否有资格使用 FLT3 抑制剂。由于体细胞和种系突变都可以在肿瘤组织中通过高通量测序来识别，因此尽可能区分这些改变的来源变得很重要——特别是在这种具有挑战性的情况下，要确定治疗方式。同时进行肿瘤/种系测序可以识别罕见的种系突变，并有助于确定它们在疾病发病机制中的意义。
