Faculty of Medicine, Masaryk University, Brno, 625 00, Czech Republic.
Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, 625 00, Czech Republic.
J Cancer Res Clin Oncol. 2018 Jul;144(7):1239-1251. doi: 10.1007/s00432-018-2652-2. Epub 2018 May 2.
This study aimed at analyzing the association of gene mutations and other acute myeloid leukemia (AML) characteristics with engraftment outcomes in immunodeficient mice and to select the engraftment outcomes that best reflect patient survival.
Mutations in 19 genes as well as leukemia- and patient-related characteristics were analyzed for a group of 47 de novo AML samples with respect to three engraftment outcomes: engraftment ability, engraftment intensity (percentage of hCD45 cells) and engraftment latency. Leukemia-related characteristics were additionally analyzed in an extended group of 68 samples that included the 47 de novo samples, and additional 21 samples from refractory and relapsed cases. Engraftment outcomes were compared with overall and event-free survival of the patients.
For the 47 de novo samples, no single mutation influenced engraftment, whereas the NPM1 /DNMT3A co-mutation was associated with higher engraftment ability. NPM1 /FLT3-ITD had lower engraftment intensity. Among leukemia-related characteristics, a complex karyotype was associated with higher engraftment intensity. Among patient-related characteristics, higher cytogenetic risk was associated with higher engraftment intensity, and failure to achieve clinical remission was associated with shorter engraftment latency. In the extended group of 68 samples, white blood count was associated with higher engraftment ability, and the presence of a complex karyotype was associated with higher engraftment intensity. Association with patient overall survival was seen only for engraftment intensity.
The engraftment of AML was influenced by mutation-interactions and other AML characteristics, rather than by single mutated genes, and engraftment intensity best reflected clinical penetrance of AML.
本研究旨在分析基因突变和其他急性髓系白血病（AML）特征与免疫缺陷小鼠植入结果的关系，并选择最能反映患者生存情况的植入结果。
分析了 47 例新发 AML 样本中 19 个基因的突变以及与白血病和患者相关的特征，这些样本与三种植入结果有关：植入能力、植入强度（hCD45 细胞的百分比）和植入潜伏期。在一个扩展组的 68 个样本中，包括 47 个新发样本和另外 21 个难治性和复发病例，还分析了白血病相关特征。将植入结果与患者的总生存率和无事件生存率进行比较。
对于 47 个新发样本，没有单个突变影响植入，而 NPM1 /DNMT3A 共突变与更高的植入能力相关。NPM1 /FLT3-ITD 具有较低的植入强度。在白血病相关特征中，复杂核型与更高的植入强度相关。在患者相关特征中，更高的细胞遗传学风险与更高的植入强度相关，未能达到临床缓解与更短的植入潜伏期相关。在 68 个扩展样本中，白细胞计数与更高的植入能力相关，而复杂核型与更高的植入强度相关。只有植入强度与患者的总生存率相关。
AML 的植入受到突变相互作用和其他 AML 特征的影响，而不是单个突变基因的影响，植入强度最能反映 AML 的临床侵袭性。
