Prognostic significance of diagnosed WT1 level in acute myeloid leukemia: a meta-analysis

Abstract

The Wilms' tumor 1 (WT1) expression has been recognized in a substantial number of acute myeloid leukemia (AML) patients. Some studies indicated the association of diagnosed WT1 higher expression (WT1(H)) and poor outcome in the AML patients, while other studies had different opinions. Therefore, we performed a meta-analysis to evaluate the controversial prognostic significance of diagnosed WT1(H) in AML. Eligible studies were identified from several databases including PubMed, Embase, Web of Science, and the Cochrane Library (up to September 2014). The primary end point was overall survival (OS) and disease-free survival (DFS) was chosen as secondary end point. If possible, we would pool estimate effects (hazard ratio [HR] with 95 % confidence interval [CI]) of outcomes in both fixed and random effects models. Eleven studies, covering 1497 AML patients, were included in this meta-analysis. Pooled HRs indicated that diagnosed WT1(H) had a poor impact on the survival of AML patients (HR for OS, 1.37; HR for DFS, 1.38). Furthermore, diagnosed WT1(H) appeared to be an adverse prognostic indicator in adult AML (HR for OS, 1.43; HR for DFS, 1.41) and non-promyelocytic AML (non-M3 AML) (HR for OS, 1.46; HR for DFS, 1.41). Diagnosed WT1(H) had slightly but significantly poor prognostic impact on OS and DFS of patients with AML in total population and some specific subgroups.

<b><i>Wilms Tumor 1 </i></b><b>(</b><b><i>WT1</i></b><b>)</b> mRNA Expression Level at Diagnosis Is a Significant Prognostic Marker in Elderly Patients with Myelodysplastic Syndrome

“…Moreover, WT1 expression can be used to detect minimal residual disease after HSCT [20]. However, although a recent meta-analysis was consistent with these previous reports, concluding that a higher WT1 expression had a slight poor prognostic impact on OS and disease-free survival [23], some studies did not find a relationship between WT1 expression at diagnosis and OS or event-free survival in AML patients [21,22]. There are 3 previous reports addressing the association between WT1 expression and prognosis for MDS patients [7,24,25].…”

Immune responses to WT1 in patients with AML or MDS after chemotherapy and allogeneic stem cell transplantation

“…WT1‐expressing AML patients who achieve a CR turn WT1 negative, whereas persistence of WT1 indicates a treatment failure . WT1 has been proposed as a MRD marker in AML ,.…”

“…Usually patients who reach complete remission (CR) turn WT1 negative, whereas persistence of WT1 indicates treatment failure . This has recently been confirmed in a meta‐analysis …”

“…9,16 This has recently been confirmed in a meta-analysis. 17 Here, we assessed the expression of WT1 and the presence of WT1-specific T cells reacting against this LAA in patients with AML or MDS before and after conventional chemotherapy and allogeneic SCT. In our study, WT1 was defined a valuable MRD marker.…”

A gene expression signature for defining aggressive phenotype and prognosis in intermediate-risk acute myeloid leukemia

“…For example, mutations of CEBPA and NPM1 are associated with favorable outcomes (Ahn et al 2016;Han et al 2013;Li et al 2015), whereas mutations of FLT3-ITD, WT1, MLL, TET2 and DNMT3A are associated with an unfavorable clinical outcome (Ley et al 2010;Mikulasova et al 2010;Ribeiro et al 2012;Stirewalt & Radich 2003). High expression of WT1, ERG, and DNMT3B as well as low expression of LEF1 have also been shown to be unfavorable prognostic factor (Metzeler et al 2009;Metzeler et al 2012;Schulze et al 2016;Yi-Ning et al 2015). However, none of the present classification strategies conform to clinical needs entirely, which suggests that a more complete and accurate understanding of the genetic …”