Acute myeloid leukemia (AML) is typically characterized clinically for prognostic purposes using both cytogenetic and molecular characteristics. However, both cytogenetic and molecular risk stratification schemas are varied and few reports have studied correlations between these schemas. We have performed a single institution retrospective review of cytogenetic and molecular classifications of AMLs seen at Penn Medicine between 2013 and 2018. One-hundred fourty-four cases were characterized according to European Leukemia Net (ELN) or Medical Research Council (MRC) criteria for cytogenetics and results compared to molecular profiling. When we analyzed the most common sequencing study results within the risk groupings, negative sequencing studies and FLT3 mutations were common in favorable AMLs, intermediate AMLs had mutations in FLT3, NPM1, DNMT3A and IDH2, while adverse AMLs had a high prevalence of TP53 mutations. We next grouped the genes on the panel by their proteins’ functions and found mutations in signaling pathway genes to be common in favorable AMLs while tumor suppressors were commonly mutated in adverse AMLs. AMLs grouped by the type of chromosomal abnormality present showed that FLT3 mutations were common in AMLs with a trisomy while TP53 mutations were common in AMLs with a monosomy or a deletion. TP53 mutations are especially common in AMLs with a monosomal karyotype and often overlap with 17p loss. Interestingly, although all AMLs with TP53 mutations have a defect in the response to DNA damage, expression of P53 protein before and after irradiation is not consistently predicted by phenotype. Overall, these studies confirm the genetic complexity of AML which does not fall into simple patterns of cooperating mutations.

急性髓性白血病 (AML) 通常使用细胞遗传学和分子特征在临床上表征以用于预后目的。然而，细胞遗传学和分子风险分层模式各不相同，很少有报告研究这些模式之间的相关性。我们对 2013 年至 2018 年期间在 Penn Medicine 看到的 AML 的细胞遗传学和分子分类进行了单一机构回顾性审查。 144 例病例的特征是根据欧洲白血病网 (ELN) 或医学研究委员会 (MRC) 标准细胞遗传学和结果与分子谱比较。当我们分析风险分组中最常见的测序研究结果时，阴性测序研究和FLT3突变在有利的 AML 中很常见，中间 AML 在FLT3、NPM1、DNMT3A和IDH2 中有突变，而不利的 AML 有很高的TP53突变发生率。我们接下来根据蛋白质的功能对面板上的基因进行分组，并发现信号通路基因的突变在有利的 AML 中很常见，而肿瘤抑制基因在不利的 AML 中通常会发生突变。按存在的染色体异常类型分组的 AML 显示，FLT3突变在具有三体性的 AML 中很常见，而TP53突变在具有单体或缺失的 AML 中很常见。TP53突变在具有单体核型的 AML 中特别常见，并且经常与 17p 丢失重叠。有趣的是，尽管所有具有TP53突变的AML对 DNA 损伤的反应都有缺陷，但表型并不能一致地预测照射前后 P53 蛋白的表达。总的来说，这些研究证实了 AML 的遗传复杂性，它不属于简单的合作突变模式。