Wilms’ Tumor Gene (WT1) Expression and Minimal Residual Disease in Acute Myeloid Leukemia

Abstract

Copyright: The Authors.Licence: This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Users are allowed to share (copy and redistribute the material in any medium or format) and adapt (remix, transform, and build upon the material for any purpose, even commercially), as long as the authors and the publisher are explicitly identified and properly acknowledged as the original source. AbstractThe identification of minimal residual disease (MRD) has led to substantial improvements in early recognition of the recurrence of acute myeloid leukemia (AML). Flow cytometry (FC), real-time quantitative polymerase chain reaction (RQ-PCR) and fluorescence in situ hybridization are useful methods for the detection of MRD in AML patients although molecular monitoring of leukemia-specific rearranged (RUNX1-RUNX1T1 and CBFB-MYH11) or mutated genetic (NPM1, CEBPA) sequences represents the most sensitive methodology. Rossi et al. 274Besides, more than 50% of all AML patients lack one of these specific sequences, so it is crucial to identify molecular targets applicable for the majority of patients. WT1 is overexpressed at the mRNA level in 80-90% of AML cases at diagnosis in both peripheral blood and bone marrow, and is detectable in a consistent low range in normal donors. These features have led to its adoption for MRD detection using RQ-PCR. A European LeukemiaNet Study found the magnitude of WT1 log reduction after induction chemotherapy to be an independent predictor of relapse. Other studies showed a poorer outcome in patients having WT1 levels above reference thresholds at specific time points. WT1 expression was compared with other modalities of MRD assessment, such as RQ-PCR of specific fusion genes and FC, but no differences in terms of predictive value emerged. Finally, some authors translated the use of WT1 in the clinic giving donor lymphocytes infusions to patients with increasing WT1-mRNA levels after allogeneic stem cell transplantation and obtaining an improvement of survival in this subset. Data collected on WT1 expression over the past years provided evidence for the use of this molecular marker to stratify high-risk AML patients. It can also be used as a marker for early interventional therapy, but further studies are needed to demonstrate it.

EGR-mediated control of STIM expression and function

“…Further, statins inhibit EGR1 expression in atherosclerotic lesions [138], further supporting the existence of a link between EGR1 expression and atherosclerosis. EGR1 expression in vascular smooth muscle cells (VSMCs) is primarily driven by NADPH-dependent heme oxidation, amongst other things [139, 140]. These observations support the notion EGR1 target genes are involved in cellular responses to oxidative conditions.…”

Identification and prognosis analysis of germline WT1 (p.Arg370Pro) and TET2 (p.Asp1844Asn) mutations in an acute myeloid leukemia patient with t(9;11)(p21.3;q23.3);KM2TA-MLL3 

“…From a molecular point of view, this may be a reasonable explanation for the disease. In clinical practice, WT1 expression and disease progression are usually parallel to each other; WT1 expression is also used as the MRD marker of hematological neoplasms when other genetic alterations are absent [17]. However, in this case, abnormal up-regulation of WT1 was not observed at different stages, but the WT1 mutation persisted.…”

Construction of a 14‑lncRNA risk score system predicting survival of children with acute myelocytic leukemia

“…The Wilms' tumor gene 1 (WT1) is overexpressed in AML and functions as an oncogene (34). Therefore, it is a therapeutic target of AML.…”