Rondoni Michela, Marconi Giovanni, Nicoletti Annalisa, Giannini Barbara, Zuffa Elisa, Giannini Maria Benedetta, Mianulli Annamaria, Norata Marianna, Monaco Federica, Zaccheo Irene, Rocchi Serena, Zannetti Beatrice Anna, Santoni Adele, Graziano Claudio, Bocchia Monica, Lanza Francesco
UO Ematologia, Ospedale S. Maria delle Croci, Via Randi 5, 48121 Ravenna, Italy.
Department of Medicine and Surgery (DIMEC), University of Bologna, 40126 Bologna, Italy.
Cancers (Basel). 2025 Apr 3;17(7):1213. doi: 10.3390/cancers17071213.
Wilms' tumor gene 1 () is a critical player in acute myeloid leukemia (AML), often serving as a biomarker for measurable residual disease (MRD). The gene 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. We analyzed 34 AML patients with low expression (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. 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 in , , and , were present in most patients with low WT1 expression. All but one case of - or -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. Low WT1 expression in AML is associated with a distinct and complex mutational profile, marked by frequent CHIP and MR mutations.
威尔姆斯瘤基因1（WT1）是急性髓系白血病（AML）中的关键因子，常作为可测量残留病（MRD）的生物标志物。WT1基因在大多数AML病例诊断时过度表达，与预后明显无关，同时其在低水平表达患者中的作用仍不明确。本研究调查了诊断时WT1低表达的AML患者的突变图谱和临床结局。我们分析了2013年至2017年在三家机构诊断和治疗的34例WT1低表达（WT1/ABL1<250）的AML患者。采用二代测序（NGS）研究AML中32个常见突变基因的突变状态。将特定突变的存在情况以及临床结局与一般AML人群进行比较。与一般AML人群相比，WT1低表达的患者显示出显著更高的突变负担，每位患者的中位突变数为3.4个。值得注意的是，大多数WT1低表达患者存在克隆性造血（CHIP）或骨髓发育异常相关（MR）突变，特别是在DNMT3A、TET2和ASXL1基因中。WT1低表达队列中除1例以外的所有NPM1 -或FLT3 -突变AML病例都存在更多CHIP或MR突变。WT1低表达的患者的总生存期（OS）与MR AML预期的OS相当。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。
