Real-Time Quantitative Polymerase Chain Reaction Detection of Minimal Residual Disease by Standardized <i>WT1</i> Assay to Enhance Risk Stratification in Acute Myeloid Leukemia: A European LeukemiaNet Study

Cilloni, D.; Renneville, Aline; Hermitte, Fabienne; Hills, Robert Kerrin; Daly, Sarah B.; Jovanović, Jelena; Gottardi, Enrico; Fava, Milena; Schnittger, Susanne; Weiss, Tamara; Izzo, Barbara; Nomdedeu, Josep; Heijden, A. van der; Reijden, Bert A. van der; Jansen, Joop H.; Velden, Vincent H.J. van der; Ommen, Hans Beier; Preudhomme, Claude; Saglio, Giuseppe; Grimwade, David

doi:10.1200/jco.2009.22.4865

Cited by 398 publications

(446 citation statements)

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“…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: 99%

“…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%

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

et al. 2016

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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.

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Section: Introductioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…2 An added advantage of the qPCR method is that it can be standardized, as evidenced, for example, by multicenter efforts delineating the optimal control genes to include in the assays, as well as the definition of universally recognized protocols and primer designs. [3][4][5][6][7][8] Although these features constitute great advantages for the clinical integration of qPCR assays, major differences between individual laboratories in terms of variation in the qPCR procedures, together with differences in calculation of results and presentation of MRD data both in daily routine and in research, has hampered determination of the clinical use of MRD assessment in multicenter settings and the development of this technology to guide treatment approach. Given that this variability is a crucial limitation to the dissemination of this methodology, it was therefore decided under the auspices of the European LeukemiaNet (ELN) Minimal Residual Disease Work Package (WP12) to design a software package, which would enable individual centers conducting qPCR for MRD measurements to collect and express data in a standardized manner.…”

Section: Introductionmentioning

confidence: 99%

Development of standardized approaches to reporting of minimal residual disease data using a reporting software package designed within the European LeukemiaNet

et al. 2011

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“…It is now broadly accepted as marker of minimal residual disease after chemotherapy and bone marrow transplantation in acute leukemias 5.…”

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The Wilms’ tumor (WT1) gene expression correlates with the International Prognostic Scoring System (IPSS) score in patients with myelofibrosis and it is a marker of response to therapy

et al. 2016

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The Wilms tumor gene WT1 is a useful marker of clonal hematopoiesis and it has been shown to be a good marker of residual disease and it reflects the response to therapy. Although myelofibrosis is characterized by mutations of JAK2 and calreticulin (CALR), these mutations are not useful to monitor response to therapy. In this study we demonstrated that in patients affected by myelofibrosis WT1 correlates with the International Prognostic Scoring System (IPSS) score at diagnosis. Furthermore WT1 is a good marker of response to JAK2 inhibitors especially for patients without blasts and for patients who develop anemia or thrombocytopenia not for progression but as therapy related toxicity. Finally, WT1 transcript reduction can mirror a benefit of therapy on the disease burden. This study demonstrated that WT1 is a good marker for monitoring the response to therapy in patients affected by myelofibrosis.

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Real-Time Quantitative Polymerase Chain Reaction Detection of Minimal Residual Disease by Standardized WT1 Assay to Enhance Risk Stratification in Acute Myeloid Leukemia: A European LeukemiaNet Study

Cited by 398 publications

References 45 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

Development of standardized approaches to reporting of minimal residual disease data using a reporting software package designed within the European LeukemiaNet

The Wilms’ tumor (WT1) gene expression correlates with the International Prognostic Scoring System (IPSS) score in patients with myelofibrosis and it is a marker of response to therapy

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