The association of level of reduction of Wilms’ tumor gene 1 mRNA transcript in bone marrow and outcome in acute myeloid leukemia patients

Shibasaki, Yasuhiko; Seki, Yoshinobu; Tanaka, Tomoyuki; Miyakoshi, Syukuko; Fuse, Kyoko; Kozakai, Takashi; Kobayashi, Hironori; Ushiki, Takashi; Abe, Takashi; Yano, Toshio; Matsushima, Masato; Kobayashi, Takashi; Isahai, Noriatsu; Takizawa, Jun; Narita, Miwako; Koyama, Satoshi; Furukawa, Tatsuo; Sone, Hirohito; Masuko, Masayoshi

doi:10.1016/j.leukres.2015.03.021

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…In the end, we cannot say that one is clearly better than the other and we have seen that both methods are useful to stratify patients at high risk of relapse as similarly reported by other Authors [32][33][34]. These results have been confirmed by other groups, who reported the power of WT1 monitoring in detecting patients at high risk of relapse, but no conclusive data are available concerning the cut-off for positive versus negative samples, as well as the optimal time-point for its assessment [23,[36][37][38][39][40][41][42][43]. Concerning this latter point, data coming from the published studies are not conclusive.…”

Section: Discussionsupporting

confidence: 72%

“…Concerning this latter point, data coming from the published studies are not conclusive. In particular, a very early time-point for WT1 monitoring (postinduction) [15,35,[36][37][38][39][41][42][43], but also a later time-point (postconsolidation or pre-allo-SCT) [38,[41][42][43] have been reported to significantly predict the outcome. Concerning LAIP-MFC sensitivity and efficiency, our data are concordant with those reported by the GIMEMA group and suggest that the most accurate predictive time-point of MRD assessment is probably after consolidation [14,44].…”

Section: Discussionmentioning

confidence: 99%

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Postremission sequential monitoring of minimal residual disease by WT1 Q‐PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk‐adapted therapy in acute myeloid leukemia patients

et al. 2015

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Risk stratification in acute myeloid leukemia (AML) patients using prognostic parameters at diagnosis is effective, but may be significantly improved by the use of on treatment parameters which better define the actual sensitivity to therapy in the single patient. Minimal residual disease (MRD) monitoring has been demonstrated crucial for the identification of AML patients at high risk of relapse, but the best method and timing of MRD detection are still discussed. Thus, we retrospectively analyzed 104 newly diagnosed AML patients, consecutively treated and monitored by quantitative polymerase chain reactions (Q‐PCR) on WT1 and by multiparametric flow cytometry (MFC) on leukemia‐associated immunophenotypes (LAIPs) at baseline, after induction, after 1st consolidation and after 1st intensification. By multivariate analysis, the factors independently associated with adverse relapse‐free survival (RFS) were: bone marrow (BM)‐WT1 ≥ 121/104 ABL copies (P = 0.02) and LAIP ≥ 0.2% (P = 0.0001) (after 1st consolidation) (RFS at the median follow up of 12.5 months: 51% vs. 82% [P < 0.0001] and 57% vs. 81%, respectively [P = 0.0003]) and PB‐WT1 ≥ 16/104 ABL copies (P = 0.0001) (after 1st intensification) (RFS 43% vs. 95% [P < 0.0001]) Our data confirm the benefits of sequential MRD monitoring with both Q‐PCR and MFC. If confirmed by further prospective trials, they may significantly improve the possibility of a risk‐adapted, postinduction therapy of AML.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Postremission sequential monitoring of minimal residual disease by WT1 Q‐PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk‐adapted therapy in acute myeloid leukemia patients

et al. 2015

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“…Eighty-one distinct publications including 11 151 patients were included in this analysis (17 studies for OS, 20 studies for DFS, and 44 for both outcomes). These studies formed the basis of our statistical analyses . The characteristics of the individual studies are presented in eTable 1 in the Supplement.…”

Section: Resultsmentioning

confidence: 99%

Association of Measurable Residual Disease With Survival Outcomes in Patients With Acute Myeloid Leukemia

et al. 2020

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disease (MRD) refers to neoplastic cells that cannot be detected by standard cytomorphologic analysis. In patients with acute myeloid leukemia (AML), determining the association of MRD with survival may improve prognostication and inform selection of efficient clinical trial end points.OBJECTIVE To examine the association between MRD status and disease-free survival (DFS) and overall survival (OS) in patients with AML using scientific literature.

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“…It is known that >60% of AML patients lack specific molecular targets, and it is therefore important to identify alternative molecular markers applicable for the majority of AML patients ( 13 ). Retrospective analysis of cohorts of previous studies identified that quantification of WT1 mRNA in BM specimens may be used as a marker of MRD and predict a relapse of AML after allogeneic HSCT ( 14 , 15 ). Marjanovic et al ( 16 ) confirmed that WT1 transcript levels were associated with clinical remission and relapse.…”

Section: Discussionmentioning

confidence: 99%

Combined usage of Wilms' tumor gene quantitative analysis and multiparameter flow cytometry for minimal residual disease monitoring of acute myeloid leukemia patients after allogeneic hematopoietic stem cells transplantation

Hao

Cheng

et al. 2017

Exp Ther Med

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High expression of the Wilms' tumor gene (WT1) in acute myeloid leukemia (AML) has been considered as a sensitive marker of minimal residual disease (MRD). The present study investigated the significance of quantitative analysis of WT1 mRNA, combined with multiparameter flow cytometry (MFC) regarding its efficacy and prognostic as well as relapse prediction value for leukemia patients with hematopoietic stem cell transplantation. Reverse-transcription quantitative polymerase chain reaction analysis demonstrated that the expression of WT1 in the initial and relapse group was significant higher than that in the complete remission (CR) group (P<0.01). WT1 and the donor chimerism were negatively correlated (r=−0.73, P<0.05). In all AML patients, WT1 was the highest in the M3 subtype and the lowest in the M1 subtype. Follow-up of 12 AML patients demonstrated that WT1 gene expression levels markedly decreased after CR, but obviously increased after relapse, as did the rate of the leukemia cells detected by MFC. The combined usage of MFC and WT1 monitoring contributed to an improved detection rate of relapse (91.7%), and may be used to monitor MRD, assess the treatment efficacy and prognosis, and predict the risk of recurrence in leukemia patients without specific molecular markers after allogeneic hematopoietic stem cell transplantation.

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The association of level of reduction of Wilms’ tumor gene 1 mRNA transcript in bone marrow and outcome in acute myeloid leukemia patients

Cited by 7 publications

References 23 publications

Postremission sequential monitoring of minimal residual disease by WT1 Q‐PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk‐adapted therapy in acute myeloid leukemia patients

Postremission sequential monitoring of minimal residual disease by WT1 Q‐PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk‐adapted therapy in acute myeloid leukemia patients

Association of Measurable Residual Disease With Survival Outcomes in Patients With Acute Myeloid Leukemia

Combined usage of Wilms' tumor gene quantitative analysis and multiparameter flow cytometry for minimal residual disease monitoring of acute myeloid leukemia patients after allogeneic hematopoietic stem cells transplantation

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