Dynamic changes in the level of WT1 as an MRD marker to predict the therapeutic outcome of patients with AML with and without allogeneic stem cell transplantation

Abstract

Monitoring minimal residue disease (Mrd) is an effective approach to evaluate the response to chemotherapy, and it is used to select the ideal therapeutic strategy and to predict the recurrence during therapy for hematological disorders. The Wilm's tumor 1 (WT1) gene, which is highly expressed in >80% of patients with acute myeloid leukemia (aMl) and its increased expression level may cause poor clinical outcomes, is a potential Mrd marker of hematological neoplasms. in the present study, the expression levels of WT1 and other molecular markers were retrospectively analyzed by reverse transcription-quantitative Pcr in 195 patients with AML. The expression level of WT1 was significantly lower in patients with remission compared with patients with early-stage and recurrent AML. Moreover, WT1 expression was significantly decreased in patients with runX family transcription factor 1-runX1 translocation partner 1 fusion, but higher in patients with promyelocytic leukemia-retinoic acid receptor α fusion. WT1 expression was significantly reduced during remission. in patients with aMl who underwent allogeneic hematopoietic stem cell transplantation (allo-HScT), the mortality rate 2 years after allo-HSCT was significantly lower in patients with low expression level of WT1 compared with subjects presenting high expression level of WT1. collectively, the upregulation of the expression level of WT1 in combination with the identification of other genetic abnormalities may be used as Mrd markers of hematological neoplasms.

Prognostic impact of peripheral blood WT1 mRNA dynamics in patients with acute myeloid leukemia treated with venetoclax combination therapy

“…In addition, WT1 mRNA value positivity (≥ 50 copies/µg RNA) in PB after intensive chemotherapy or stem cell transplantation is an independent poor prognostic factor for relapse [ 24 – 28 ]. Therefore, WT1 mRNA value after chemotherapy can indicate disease activities such as remission and relapse [ 29 ]. This study also found that WT1 mRNA 1-log reduction by the end of cycle 2 and WT1 mRNA value negativity during the treatment cycle were associated with significantly prolonged OS and EFS.…”

Significance of WT1 and multiparameter flow cytometry assessment in patients with chronic myelomonocytic leukemia receiving allogeneic hematopoietic stem cell transplantation

“…Approximately 50% of patients with CMML do not receive chemotherapy before transplantation; hence, MRD monitoring in CMML and AML also differs. Previous studies have reported that WT1 is overexpressed in >80% of patients with AML and could be used as a marker of recurrence after achieving complete remission 31,32 . However, WT1 has not been used as an established marker for MRD monitoring in patients with CMML.…”

“…Previous studies have reported that WT1 is overexpressed in >80% of patients with AML and could be used as a marker of recurrence after achieving complete remission. 31,32 However, WT1 has not been used as an established marker for MRD monitoring in patients with CMML. FCM could distinguish abnormal immunophenotypic patterns expressed on leukemic cells.…”

Novel combined variants of WT1 and TET2 in a refractory and recurrent AML patient

“…However, in this case, abnormal up-regulation of WT1 was not observed at different stages, but the WT1 variant persisted. Similar to the WT1 mutation being related to poor prognosis [ 14 ], WT1 overexpression was also indicated to be associated with shorter OS [ 15 ]. However, the question remains, which alteration could be a potential indicator of prognostic stratification for the patient; expression level or mutation status?…”