Background:Wilms’ tumor gene 1 (WT1) is a critical player in acute myeloid leukemia (AML), often serving as a biomarker for measurable residual disease (MRD). TheWT1gene is overexpressed in the majority of AML cases at diagnosis, with apparently no correlation with prognosis, and in the meantime, its role in patients with low-level expression is still undefined. This study investigates the mutational landscape and clinical outcomes of AML patients with low WT1 expression at diagnosis.Methods:We analyzed 34 AML patients with lowWT1expression (WT1/ABL1 < 250) diagnosed and treated from 2013 to 2017 at three institutions. Next-generation sequencing (NGS) was employed to investigate the mutational status of 32 genes commonly mutated in AML. The presence of specific mutations, as well as clinical outcomes, was compared to the general AML population.Results:Patients with low WT1 expression showed a significantly higher mutational burden, with a median of 3.4 mutations per patient, compared to the general AML population. Notably, clonal hematopoiesis (CHIP) or myelodysplasia-related (MR) mutations, particularly inASXL1,TET2, andSRSF2, were present in most patients with low WT1 expression. All but one case ofNPM1- orFLT3-mutant AML in the low-WT1 cohort harbored more CHIP or MR mutations. Patients with low WT1 expression had an overall survival (OS) that was superimposable to the OS expected in MR AML.Conclusions:Low WT1 expression in AML is associated with a distinct and complex mutational profile, marked by frequent CHIP and MR mutations.
背景：Wilms肿瘤基因1（WT1）在急性髓系白血病（AML）中扮演关键角色，常作为可测量残留病（MRD）的生物标志物。WT1基因在诊断时的大多数AML病例中过度表达，但似乎与预后无关，同时其在低表达患者中的作用尚未明确。本研究旨在探讨诊断时WT1低表达的AML患者的突变谱和临床结局。 方法：我们分析了2013年至2017年间在三家机构诊断并治疗的34例WT1低表达（WT1/ABL1 < 250）的AML患者。采用下一代测序（NGS）技术，研究了32个在AML中常见突变的基因的突变状态。将特定突变的存在以及临床结局与一般AML人群进行比较。 结果：与一般AML人群相比，WT1低表达患者的突变负荷显著更高，每位患者的中位突变数为3.4个。值得注意的是，克隆性造血（CHIP）或骨髓增生异常相关（MR）突变，尤其是在ASXL1、TET2和SRSF2基因中，在大多数WT1低表达患者中存在。在低WT1队列中，除一例外，所有NPM1或FLT3突变的AML病例均携带更多的CHIP或MR突变。WT1低表达患者的总生存期（OS）与MR AML的预期OS相似。 结论：AML中WT1低表达与独特且复杂的突变谱相关，其特征是频繁出现CHIP和MR突变。
Low WT1 Expression Identifies a Subset of Acute Myeloid Leukemia with a Distinct Genotype
肿瘤(癌症)患者之家