<i>WT1</i> gene expression: an excellent tool for monitoring minimal residual disease in 70% of acute myeloid leukaemia patients – results from a single‐centre study

Østergaard, Mette; Olesen, Lene; Hasle, Henrik; Kjeldsen, Eigil; Hokland, Peter

doi:10.1111/j.1365-2141.2004.04952.x

Cited by 173 publications

(165 citation statements)

References 36 publications

Supporting

Mentioning

145

Contrasting

Unclassified

Order By: Relevance

“…Similarly, Galimberti et al (12) showed a higher probability of disease progression in AML patients presenting high WT1 levels, and recently, Nomdedeu et al (13) also confirmed the prognostic role of high WT1 levels at diagnosis in a larger study population. However, these data are in contrast with results reported by others where WT1 levels did not correlate with the outcome (8)(9)(10)14), thus suggesting a controversial role for WT1 expression at presentation. On the contrary, a greater agreement was found among groups that have used WT1 levels as a marker of minimal residual disease (MRD) in AML remission BMs (less than 5% of blast cells).…”

Section: Introductioncontrasting

confidence: 57%

“…Besides, WT1 is highly overexpressed in the BM or peripheral blood (PB) of a variety of leukemias, and these evidences support the role of WT1 as an oncogene in this subset (6,7). Increased levels of WT1 expression can be found in both acute lymphoblastic and acute myeloid leukemia (AML) although more frequently in AML (frequencies varying from 73% to 91%) (8)(9)(10). Following the discovery of overexpression of WT1, there has been growing evidence that the WT1 expression levels may have a prognostic role in AML.…”

Section: Introductionmentioning

confidence: 99%

“…On the contrary, a greater agreement was found among groups that have used WT1 levels as a marker of minimal residual disease (MRD) in AML remission BMs (less than 5% of blast cells). In particular, WT1 expression has been shown to predict disease progression in AML patients treated with conventional chemotherapy (8)(9)(10)(15)(16)(17) and patients undergone allogeneic stem cell transplantation (allo-SCT) (18)(19)(20)(21)(22). Furthermore, when WT1 expression was compared with widely used techniques in monitoring MRD such as multiparameter flow cytometry (MFC) (23) or specific molecular targets such as fusion genes transcripts (PMLRARa, AML-ETO1, and CBFb-MYH11), comparable sensitivities were found in predicting the relapse in AML.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2016

View full text Add to dashboard Cite

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.

show abstract

Section: Introductioncontrasting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2016

View full text Add to dashboard Cite

show abstract

“…These findings have been previously described and are in concordance with results of other studies. [47][48][49][50][51][52][53][54][55] WT1 isoform expression patterns showed at first glance subtle but significant differences among normal BM, AML and MDS, and also between childhood and adult samples. These specific patterns enabled the clustering of samples into groups representing the individual diagnoses.…”

Section: Discussionmentioning

confidence: 99%

Real-time PCR quantification of major Wilms’ tumor gene 1 (WT1) isoforms in acute myeloid leukemia, their characteristic expression patterns and possible functional consequences

et al. 2012

View full text Add to dashboard Cite

Wilms' tumor gene 1 (WT1) functions including some contradictory effects may be explained by the presence and interactions of its isoforms, however, their evaluation has been so far complicated by several technical problems. We designed unique quantitative PCR systems for direct quantification of the majorand verified their sensitivity, specificity and reproducibility in extensive testing. With this method we evaluated WT1 total and isoform expression in 23 normal bone marrow (BM) samples, 73 childhood acute myeloid leukemia (AML), 20 childhood myelodysplastic syndrome (MDS), 9 childhood severe aplastic anemia (SAA), 30 adult AML and 29 adult MDS patients. WT1 isoform patterns showed differences among these samples and clustered them into groups representing the specific diagnoses (Po0.0001). Isoform profiles were independent of total WT1 expression and possess certain common features-overexpression of isoform D and

show abstract

“…8 WT1 expression has been evaluated as a marker for risk stratification and MRD detection in AML. [1][2][3][4][5][11][12][13][14] However, contradictory reports refer to the value of WT1 hyperexpression for monitoring MRD during front-line chemotherapy and after allogeneic stem-cell transplantation. Although many authors describe a strong predictive value, 3,4,9,10,15 these findings could not be confirmed by others.…”

Section: Introductionmentioning

confidence: 99%

Standardization of WT1 mRNA quantitation for minimal residual disease monitoring in childhood AML and implications of WT1 gene mutations: a European multicenter study

Willasch

Gruhn²,

Coliva

et al. 2009

Leukemia

View full text Add to dashboard Cite

A standardized, sensitive and universal method for minimal residual disease (MRD) detection in acute myeloid leukemia (AML) is still pending. Although hyperexpression of Wilms' tumor (WT1) gene transcript has been frequently proposed as an MRD marker in AML, wide comparability of the various methods used for evaluating WT1 expression has not been given. We established and standardized a multicenter approach for quantifying WT1 expression by quantitative reverse transcriptase PCR (qRT-PCR), on the basis of a primer/probe set combination at exons 6 and 7. In a series of quality-control rounds, we analyzed 69 childhood AML samples and 47 normal bone marrow (BM) samples from 4 participating centers. Differences in the individual WT1 expressions levels ranged within o0.5 log of the mean in 82% of the cases. In AML samples, the median WT1/1E þ 04 Abelson (ABL) expression was 3.5E þ 03 compared with that of 2.3E þ 01 in healthy BM samples. As 11.5% of childhood AML samples in this cohort harbored WT1 mutations in exon 7, the effect of mutations on WT1 expression has been investigated, showing that mutated cases expressed significantly higher WT1 levels than wild-type cases. Hence, our approach showed high reproducibility and applicability, even in patients with WT1 mutations; therefore, it can be widely used for the quantitation of WT1 expression in future clinical trials.

show abstract

WT1 gene expression: an excellent tool for monitoring minimal residual disease in 70% of acute myeloid leukaemia patients – results from a single‐centre study

Cited by 173 publications

References 36 publications

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

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

Real-time PCR quantification of major Wilms’ tumor gene 1 (WT1) isoforms in acute myeloid leukemia, their characteristic expression patterns and possible functional consequences

Standardization of WT1 mRNA quantitation for minimal residual disease monitoring in childhood AML and implications of WT1 gene mutations: a European multicenter study

Contact Info

Product

Resources

About