WT1 Expression in Peripheral Blood at Diagnosis and During the Course of Early Consolidation Treatment Correlates With Survival in Patients With Intermediate and Poor-Risk Acute Myeloid Leukemia

Šálek, Cyril; Vydra, Jan; Cerovská, Ela; Šestáková, Šárka; Ransdorfova, Sarka; Válková, Veronika; Cetkovský, Petr; Remešová, Hana

doi:10.1016/j.clml.2020.07.014

Cited by 6 publications

(3 citation statements)

References 34 publications

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“…Several studies have shown that a 1-log reduction in WT1 mRNA value in PB is a predictor of relapse-free survival and a 2-log or greater reduction in WT1 mRNA value is associated with significantly better OS [ 13 – 15 ]. 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 ].…”

Section: Discussionmentioning

confidence: 99%

“…WT1 mRNA is overexpressed at least 80% of patients with AML and can be universally used as an MRD marker, even in patients with AML who are not eligible for leukemia-specific polymerase chain reaction (PCR) assays (e.g., for NPM1, PML-RARA, or CBF AML) [ 11 , 12 ]. Several studies have shown that high PB WT1 mRNA values after treatment of AML are associated with relapse and poor prognosis [ 13 – 15 ]. However, the usefulness of PB WT1 mRNA quantification as a predictor of long-term prognosis in VEN combination therapy for AML has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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

Sato,

Kobayashi,

Kameoka

et al. 2024

Int J Clin Oncol

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Background Wilms' tumor gene 1 (WT1) mRNA quantification is a useful marker of measurable residual disease in acute myeloid leukemia (AML). However, whether monitoring the WT1 mRNA levels may predict the outcome of venetoclax (VEN) combination therapy in AML is not reported. This study aims to elucidate whether WT1 mRNA dynamics could predict long-term prognosis. Methods 33 patients with untreated or relapsed/refractory AML evaluated for peripheral blood WT1 dynamics in VEN combination therapy were analyzed. Results The median age was 73 years (range 39–87). Azacitidine was combined with VEN in 91% of patients. Overall, the median overall survival (OS) was 334 days (95% CI 210–482), and the complete remission (CR) plus CR with incomplete hematologic recovery rate was 59%. A 1-log reduction of WT1 mRNA values by the end of cycle 2 of treatment was associated with significantly better OS and event-free survival (EFS) (median OS 482 days vs. 237 days, p = 0.049; median EFS 270 days vs. 125 days, p = 0.02). The negativity of post-treatment WT1 mRNA value during the treatment was associated with significantly better OS and EFS (median OS 482 days vs. 256 days, p = 0.02; median EFS not reached vs. 150 days, p = 0.005). Multivariate analysis confirmed the significance of these two parameters as strong EFS predictors (HR 0.26, p = 0.024 and HR 0.15, p = 0.013, respectively). The increase in WT1 mRNA values was correlated with relapse. Conclusion This study demonstrates that WT1 mRNA dynamics can be a useful marker for assessing long-term prognosis of VEN combination therapy for AML.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Sato,

Kobayashi,

Kameoka

et al. 2024

Int J Clin Oncol

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“…The WT1 gene was initially identi ed as a tumor suppressor gene linked with nephroblastoma [24,25]. Over the past years, numerous studies have highlighted that WT1 is aberrantly expressed or mutated in hematopoietic malignancies, including acute leukemia (AL), myelodysplastic syndrome (MDS) and chronic myelogenous leukemia (CML) [26][27][28][29][30]. However, few data are available regarding the frequency of WT1 mutations and their impact on CEBPA mut AML.…”

Section: Discussionmentioning

confidence: 99%

Frequency and Clinical Impact of WT1 Mutations in the Context of CEBPA-Mutated Acute Myeloid Leukemia

Wang

Hua

Wang

et al. 2021

Preprint

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Introduction: Several studies have confirmed that mutations in the Wilms tumor 1 (WT1) gene occur in adult acute myeloid leukemia (AML). However, few data are available regarding the incidence of WT1 mutations in CEBPAmut AML and their impact. Methods: We retrospectively analyzed the frequency and clinical impact of WT1 mutations in 220 newly diagnosed AML patients with CEBPA mutations. Chromosome karyotype analysis was performed by R or G banding method and further confirmed either by fluorescence in situ hybridization (FISH) and/or by multiple reverse transcription polymerase chain reaction (multiple RT-PCR). Mutations were detected with a panel of 112 mutational genes using next-generation sequencing (NGS). FLT3-ITD, NPM1 and CEBPA mutation were detected by PCR Sanger sequencing.Results: Overall, 30 WT1 mutations were detected in 29 of the 220 patients (13.18%) screened. These mutations clustered overwhelmingly in exon 7 (16 mutations in 15 patients), but they were also detected in exon 8 (n=6) and exon 9 (n=8). WT1-mutated (WT1mut) patients presented with lower platelet counts (P=0.0481), higher WT1 expression (P=0.0371), and a negative trend with the M5 subtype (P=0.07) compared to WT wild-type (WTwt) patients. WT1 mutations were found to be significantly more frequent in AML patients with double-mutated CEBPA (CEBPAdm) than in AML patients with single-mutated CEBPA (P=0.043). Of note, the concomitant mutations in epigenetic regulators were inversely correlated with WT1 mutations (P=0.003). Patients with newly diagnosed WT1mut AML had inferior relapse-free survival, event-free survival and overall survival compared with patients with WT1wt AML (P=0.002, 0.004, and 0.010, respectively). Conclusion: Our data showed that WT1 mutations are frequently identified in CEBPAmut AML, especially in CEBPAdm AML. Patients with WT1 mutations show distinct clinical features, a spectrum of comutations, and poor prognosis compared to WT1 wild-type patients.

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Clinical values of gene alterations as marker of minimal residual disease in non-M3 acute myeloid leukemia

Chi

Wang

2021

Hematology

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WT1 Expression in Peripheral Blood at Diagnosis and During the Course of Early Consolidation Treatment Correlates With Survival in Patients With Intermediate and Poor-Risk Acute Myeloid Leukemia

Cited by 6 publications

References 34 publications

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

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

Frequency and Clinical Impact of WT1 Mutations in the Context of CEBPA-Mutated Acute Myeloid Leukemia

Clinical values of gene alterations as marker of minimal residual disease in non-M3 acute myeloid leukemia

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