Clinical features and prognosis of normal karyotype acute myeloid leukemia pediatric patients with WT1 mutations: an analysis based on TCGA database

Xu, Jing; Zhang, Yaofang; Hu, Jinjun; Ren, Yan; Wang, Hongwei

doi:10.1080/16078454.2020.1720102

Cited by 9 publications

(20 citation statements)

References 30 publications

(38 reference statements)

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“…We found longer RFS in patients with WT1 mutation. However, this result is not consistent with previous reports [ 3 , 33 , 36 , 37 ]. This may be due to the fact that previous reports were conducted in other populations or as a result of sampling error.…”

Section: Discussioncontrasting

confidence: 99%

WT1 Gene Mutations, rs16754 Variant, and WT1 Overexpression as Prognostic Factors in Acute Myeloid Leukemia Patients

Koczkodaj

Zmorzyński

Grygalewicz

et al. 2022

JCM

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(1) Background: The aim of our study was the complex assessment of WT1 variants and their expression in relation to chromosomal changes and molecular prognostic markers in acute myeloid leukemia (AML). It is the first multidimensional study in Polish AML patients; (2) Methods: Bone marrow aspirates of 90 AML patients were used for cell cultures (banding techniques and fluorescence in situ hybridization), and to isolate DNA (WT1 genotyping, array comparative genomic hybridization), and RNA (WT1 expression). Peripheral blood samples from 100 healthy blood donors were used to analyze WT1 rs16754; (3) Results: Allele frequency and distribution of WT1 variant rs16754 (A;G) did not differ significantly among AML patients and controls. Higher expression of WT1 gene was observed in AA genotype (of rs16754) in comparison with GA or GG genotypes—10,556.7 vs. 25,836.5 copies (p = 0.01), respectively. WT1 mutations were more frequent in AML patients under 65 years of age (p < 0.0001) and affected relapse-free survival (RFS). The presence of NPM1 or CEBPA mutations decreased the risk of WT1 mutation presence, odds ratio (OR) = 0.11, 95% CI 0.02–0.46, p = 0.002 or OR = 0.05, 95% CI 0.006–0.46, p = 0.002, respectively. We observed significantly higher WT1 expression in AML CD34+ vs. CD34−, −20,985 vs. 8304 (p = 0.039), respectively. The difference in WT1 expression between patients with normal and abnormal karyotype was statistically insignificant; (4) Conclusions: WT1 gene expression and its rs16754 variant at diagnosis did not affect AML outcome. WT1 mutation may affect RFS in AML.

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Section: Discussioncontrasting

confidence: 99%

WT1 Gene Mutations, rs16754 Variant, and WT1 Overexpression as Prognostic Factors in Acute Myeloid Leukemia Patients

Koczkodaj

Zmorzyński

Grygalewicz

et al. 2022

JCM

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“…For example, variants related to drug resistance, such as NT5C2 and MSH6 , in ALL have been linked to thiopurines resistance [ 56 , 57 ]. In the same way, variants are also related to a worse prognosis with higher risk of refractoriness and relapse in AML, such as WT1 [ 58 , 59 , 60 ], or with a favourable outcome related to a better treatment response, such FBXW7 and NOTCH1 in T-ALL [ 61 , 62 , 63 ].…”

Section: Discussionmentioning

confidence: 99%

Advanced Molecular Characterisation in Relapsed and Refractory Paediatric Acute Leukaemia, the Key for Personalised Medicine

Galán-Gómez

Matamala

Ruz-Caracuel

et al. 2022

JPM

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Relapsed and refractory (R/r) disease in paediatric acute leukaemia remains the first reason for treatment failure. Advances in molecular characterisation can ameliorate the identification of genetic biomarkers treatment strategies for this disease, especially in high-risk patients. The purpose of this study was to analyse a cohort of R/r children diagnosed with acute lymphoblastic (ALL) or myeloid (AML) leukaemia in order to offer them a targeted treatment if available. Advanced molecular characterisation of 26 patients diagnosed with R/r disease was performed using NGS, MLPA, and RT-qPCR. The clinical relevance of the identified alterations was discussed in a multidisciplinary molecular tumour board (MTB). A total of 18 (69.2%) patients were diagnosed with B-ALL, 4 (15.4%) with T-ALL, 3 (11.5%) with AML and 1 patient (3.8%) with a mixed-phenotype acute leukaemia (MPL). Most of the patients had relapsed disease (88%) at the time of sample collection. A total of 17 patients (65.4%) were found to be carriers of a druggable molecular alteration, 8 of whom (47%) received targeted therapy, 7 (87.5%) of them in addition to hematopoietic stem cell transplantation (HSCT). Treatment response and disease control were achieved in 4 patients (50%). In conclusion, advanced molecular characterisation and MTB can improve treatment and outcome in paediatric R/r acute leukaemias.

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“…Risk of bias and quality assurance using the QUADAS-2 system of article assessment. Xu et al [24] Darwish et al [25] Xiao et al [26] Wang et al [27] Xu et al [28] Haubner et al [29] Abdellateif et al [30] Vollmer et al [31] Zhu et al [32] Lin et al [33] Tian et al [34] Xu et al [35] Xu et al [24] Darwish et al [25] Xiao et al [26] Wang et al [27] Xu et al [28] Haubner et al [29] Abdellateif et al [30] Vollmer et al [31] Zhu et al [32] Lin et al [33] Tian et al [34] Xu et al [35] Table 3. Risk of bias and quality assurance using the Q…”

Section: Patient Selection Interventionmentioning

confidence: 99%

“…Xu et al [24] Darwish et al [25] Xiao et al [26] Wang et al [27] Xu et al [28] Haubner et al [29] Abdellateif et al [30] Vollmer et al [31] Table 3. Risk of bias and quality assurance using the QUADAS-2 system of art Xu et al [24] Darwish et al [25] Xiao et al [26] Wang et al [27] Xu et al [28] Haubner et al [29] Abdellateif et al [30] Vollmer et al [31] Table 3. Risk of bias and quality assurance using the Q…”

Section: Studymentioning

confidence: 99%

“…Wang et al [27] Xu et al [28] Haubner et al [29] Abdellateif et al [30] Vollmer et al [31] Zhu et al [32] Lin et al [33] Tian et al [34] Xu et al [35] Basharat et al [36] Alanazi et al [37] Greiner et al [38] Shin et al [39] Dou et al [40] Padró et al [41] Assi et al [42] Table 3. Risk of bias and quality assurance using the QUADAS-2 system of art Wang et al [27] Xu et al [28] Haubner et al [29] Abdellateif et al [30] Vollmer et al [31] Zhu et al [32] Lin et al [33] Tian et al [34] Xu et al [35] Basharat et al [36] Alanazi et al [37] Greiner et al [38] Shin et al [39] Dou et al [40] Padró et al [41] Assi et al [42] Table 3. Risk of bias and quality assurance using the Q Wang et al [27] Xu et al [28] Haubner et al [29] Abdellateif et al [30] Vollmer et al [31] Zhu et al [32] Lin et al [33] Tian et al [34] Xu et al [35] Basharat et al …”

Section: ]mentioning

confidence: 99%

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A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis

Morris

Ghazi

Fletcher

et al. 2023

IJMS

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Acute myeloid leukaemia (AML) is characterized by impaired myeloid differentiation resulting in an accumulation of immature blasts in the bone marrow and peripheral blood. Although AML can occur at any age, the incidence peaks at age 65. The pathobiology of AML also varies with age with associated differences in incidence, as well as the frequency of cytogenetic change and somatic mutations. In addition, 5-year survival rates in paediatrics are 60–75% but fall to 5–15% in older AML patients. This systematic review aimed to determine whether the altered genes in AML affect the same molecular pathways, indifferent of patient age, and, therefore, whether patients could benefit from the repurposing drugs or the use of the same immunotherapeutic strategies across age boundaries to prevent relapse. Using a PICO framework and PRISMA-P checklist, relevant publications were identified using five literature databases and assessed against an inclusion criteria, leaving 36 articles, and 71 targets for therapy, for further analysis. QUADAS-2 was used to determine the risk of bias and perform a quality control step. We then priority-ranked the list of cancer antigens based on predefined and pre-weighted objective criteria as part of an analytical hierarchy process used for dealing with complex decisions. This organized the antigens according to their potential to act as targets for the immunotherapy of AML, a treatment that offers an opportunity to remove residual leukaemia cells at first remission and improve survival rates. It was found that 80% of the top 20 antigens identified in paediatric AML were also within the 20 highest scoring immunotherapy targets in adult AML. To analyse the relationships between the targets and their link to different molecular pathways, PANTHER and STRING analyses were performed on the 20 highest scoring immunotherapy targets for both adult and paediatric AML. There were many similarities in the PANTHER and STRING results, including the most prominent pathways being angiogenesis and inflammation mediated by chemokine and cytokine signalling pathways. The coincidence of targets suggests that the repurposing of immunotherapy drugs across age boundaries could benefit AML patients, especially when used in combination with conventional therapies. However, due to cost implications, we would recommend that efforts are focused on ways to target the highest scoring antigens, such as WT1, NRAS, IDH1 and TP53, although in the future other candidates may prove successful.

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Clinical features and prognosis of normal karyotype acute myeloid leukemia pediatric patients with WT1 mutations: an analysis based on TCGA database

Cited by 9 publications

References 30 publications

WT1 Gene Mutations, rs16754 Variant, and WT1 Overexpression as Prognostic Factors in Acute Myeloid Leukemia Patients

WT1 Gene Mutations, rs16754 Variant, and WT1 Overexpression as Prognostic Factors in Acute Myeloid Leukemia Patients

Advanced Molecular Characterisation in Relapsed and Refractory Paediatric Acute Leukaemia, the Key for Personalised Medicine

A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis

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