FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2070710294> ?p ?o ?g. }

• W2070710294 endingPage "454" @default.
• W2070710294 startingPage "451" @default.
• W2070710294 abstract "Mutations of Wilms’ tumour gene (WT1) are reported in 10% of acute myeloid leukemias (AML) with normal karyotype, with reduction in both relapse-free-survival and overall survival (Virappane et al, 2008). WT1 is highly expressed in acute leukemias and the myelodysplastic syndromes (MDS) (Rosenfeld et al, 2003) where it is associated with poorer prognosis (Cilloni et al, 2008; Candoni et al, 2009). About 65% of low-risk and up to 100% of high-risk MDS cases express high WT1 transcripts, correlated with higher risk of progression (Tamaki et al, 1999; Cilloni et al, 2003). To date, no studies have evaluated whether diagnostic WT1 mRNA levels influence the long-term time-to-progression (TTP) in MDS and AML. Moreover, no significant data have been produced concerning WT1 and MDS cases that have been classified according to the newer World Health Organisation Prognostic Scoring System (WPSS) score (Malcovati et al, 2007). Thus, in the present study, we evaluated the possible impact on long-term TTP exerted by WT1 mRNA levels measured at diagnosis in a series of 54 cases (24 AML and 30 MDS). WT1 transcript was quantified with the ProfileQUANT™ kit (Ipsogen, Marseille, France) on total RNA isolated using RNeasy Mini kit (QIAGEN, Valencia, CA, USA). This method estimates the ‘normal’WT1 copies/ABL1 × 104 copies ratio to be between 3 and 180. Clinical and demographic characteristics of the entire series are reported in Table I. Patients were stratified in two categories (WT1-low and -high) when the WT1 copies/ABL1 × 104 copies ratio was lower or higher than 180 respectively; the chi-square and logistic regression tests were used to assess eventual differences in clinical and demographic data. t-test was adopted for comparing mean values; Kaplan–Meier life tables were constructed for survival data and compared by means of the log-rank test, with surviving patients being censored at 15 June 2009. All statistical analyses were performed with the Statistical Package for the Social Sciences (spss) software, version 17.0 (SPSS Italia, Bologna, Italy). P values <0·05 were considered significant. All low-risk MDS patients received epoietins and/or additional blood transfusion support; the high-risk MDS group included patients who received azacitidine 75 mg/m2, 6 d a week for almost four cycles. For AML cases, induction therapy included idarubicin, less often doxorubicin with aracytin, according to the ‘3 + 7’ or ‘2 + 5’ scheme, on the basis of age (≤ or >65 years). Fourteen transplanted patients were censored before stem cell infusion. At diagnosis, WT1 expression was high in 9 out of the 30 MDS cases (30%) (four in low-risk and five in high-risk group), and in 15 of the 24 patients (62·5%) affected by AML. Mean and standard deviation values were: 333·19 WT1 copies/104ABL1 copies ± 97·89 for low-risk MDS; 551·31 copies/104ABL1 copies ± 72·02 for high-risk MDS; 2390·89 copies/104ABL1 copies 104 ± 39·92 for AML. WT1 mRNAs were significantly higher in AML when compared to both low-risk (P = 0·02) and high-risk MDS (P = 0·04). On the contrary, no significant difference in WT1 expression was found between the two risk score groups in MDS (P > 0·05). In our series of 30 MDS patients, the 36-monthTTP was 65% (median not reached at 5 years); it was not significantly affected by age, sex, performance status, white blood cell count (WBC), haemoglobin level (Hb), and platelet count (PLT) at diagnosis, blast percentage, cytogenetic features, or spleen dimension. Even the WPSS risk score in our series did not affect the TTP (36-month TTP 71% for low-risk versus 61% high-risk patients, P = 0·71). Similarly, the probability of progression was also not significantly affected by these analysed parameters. In contrast, the probability of progression was influenced by WT1 level: it was 14% for patients expressing low WT1 levels versus 56% for those with high WT1 mRNA (P = 0·03). Moreover, WT1 expression levels at diagnosis also significantly affected the 36-month TTP (Fig 1B): 73% of patients with normal WT1 expression were progression-free versus 19% of cases with elevated WT1 (P < 0·01). Noteworthy, this prognostic role of WT1 high expression was evident both in WPSS low-risk (Fig 1C) and high-risk categories (Fig 1d) (36-month TTP 78% vs. 5% in low-risk cases and 67% vs. 37% in the high-risk group; P < 0·01). Kaplan–Meier analysis of TTP in the 24 AML and 30 MDS patients. (A) TTP of the entire AML series, according to WT1 expression. P < 0·01. The y-axis shows the percentage of progression-free patients. Solid line: low WT1 levels; dotted line: high WT1 levels. P < 0·01. (B) TTP of the entire MDS series, according to WT1 expression. P < 0·01. Solid line: low WT1 levels; dotted line: high WT1 levels. P < 0·01. (C) TTP of the WPSS low-risk cases, according to WT1 expression. P < 0·01. Solid line: low WT1 levels; dotted line: high WT1 levels. P < 0·01. (D) TTP of the WPSS high-risk cases, according to WT1 expression. P < 0·01. Solid line: low WT1 levels; dotted line: high WT1 levels. P < 0·01. In AML, the 36-month TTP was 46% (median = 23 months) and was not significantly conditioned by performance status, sex, WBC, Hb, PLT at diagnosis, blast per centage, French-American-British (FAB) subtype, cytogenetic features, presence/absence of FLT3 mutations, or spleen dimension. TTP was much lower for older patients (36-month TTP 32% vs. 60% for younger patients), but it was not statistically significantly different (P = 0·12). Even in AML, the probability of progression was not significantly affected by the analysed demographic/clinical parameters. On the contrary, the probability of progression was significantly influenced by WT1 levels: 11% of patients with low WT1 levels progressed versus 80% of cases with high WT1 (P = 0·04). Moreover, in the AML series, WT1 expression levels at diagnosis did significantly affect the 36-month TTP (Fig 1A): 80% of patients with normal WT1 expression were progression-free versus 24% of cases with elevated WT1 (P = 0·01). In conclusion, the data reported above suggest that WT1 expression levels, when measured by quantitative reverse transcription polymerase chain reaction at diagnosis on bone marrow samples, could contribute to distinguish, both in MDS low- and high-risk and in AML, patients that will have a higher probability of disease progression in a shorter time interval. Interestingly, in MDS, this prognostic significance is still valid even if cases are classified according to the newer WPSS. We performed molecular assays on bone marrow samples already available for diagnostic purposes; the option of assessing WT1 on diagnostic RNAs samples would avoid further discomfort for patients. This approach, followed by the molecular monitoring of peripheral blood after chemotherapy or transplantation, would be a pursuable alternative. Undertaking this simple molecular assay at diagnosis would enable treatment to be individually tailored to each patient and allow physicians to decide how frequently WT1 levels should be monitored (or not), or whether a more intensive treatment strategy should be initiated immediately. The results of this study will need to be confirmed in a larger series of patients." @default.
• W2070710294 created "2016-06-24" @default.
• W2070710294 creator A5001285087 @default.
• W2070710294 creator A5003661727 @default.
• W2070710294 creator A5027317975 @default.
• W2070710294 creator A5029614391 @default.
• W2070710294 creator A5072006834 @default.
• W2070710294 creator A5079175426 @default.
• W2070710294 creator A5082760195 @default.
• W2070710294 date "2010-04-12" @default.
• W2070710294 modified "2023-10-17" @default.
• W2070710294 title "<i>WT1</i>expression levels at diagnosis could predict long-term time-to-progression in adult patients affected by acute myeloid leukaemia and myelodysplastic syndromes" @default.
• W2070710294 cites W2029685076 @default.
• W2070710294 cites W2033734716 @default.
• W2070710294 cites W2074269699 @default.
• W2070710294 cites W2097984158 @default.
• W2070710294 cites W2115311597 @default.
• W2070710294 cites W2148968593 @default.
• W2070710294 cites W4285719527 @default.
• W2070710294 cites W3023139340 @default.
• W2070710294 doi "https://doi.org/10.1111/j.1365-2141.2009.08063.x" @default.
• W2070710294 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20085581" @default.
• W2070710294 hasPublicationYear "2010" @default.
• W2070710294 type Work @default.
• W2070710294 sameAs 2070710294 @default.
• W2070710294 citedByCount "22" @default.
• W2070710294 countsByYear W20707102942012 @default.
• W2070710294 countsByYear W20707102942013 @default.
• W2070710294 countsByYear W20707102942015 @default.
• W2070710294 countsByYear W20707102942016 @default.
• W2070710294 countsByYear W20707102942017 @default.
• W2070710294 countsByYear W20707102942018 @default.
• W2070710294 countsByYear W20707102942019 @default.
• W2070710294 countsByYear W20707102942020 @default.
• W2070710294 countsByYear W20707102942021 @default.
• W2070710294 countsByYear W20707102942022 @default.
• W2070710294 countsByYear W20707102942023 @default.
• W2070710294 crossrefType "journal-article" @default.
• W2070710294 hasAuthorship W2070710294A5001285087 @default.
• W2070710294 hasAuthorship W2070710294A5003661727 @default.
• W2070710294 hasAuthorship W2070710294A5027317975 @default.
• W2070710294 hasAuthorship W2070710294A5029614391 @default.
• W2070710294 hasAuthorship W2070710294A5072006834 @default.
• W2070710294 hasAuthorship W2070710294A5079175426 @default.
• W2070710294 hasAuthorship W2070710294A5082760195 @default.
• W2070710294 hasBestOaLocation W20707102941 @default.
• W2070710294 hasConcept C121332964 @default.
• W2070710294 hasConcept C126322002 @default.
• W2070710294 hasConcept C143998085 @default.
• W2070710294 hasConcept C203014093 @default.
• W2070710294 hasConcept C2779282312 @default.
• W2070710294 hasConcept C2780007613 @default.
• W2070710294 hasConcept C2780817109 @default.
• W2070710294 hasConcept C2993296363 @default.
• W2070710294 hasConcept C61797465 @default.
• W2070710294 hasConcept C62520636 @default.
• W2070710294 hasConcept C71924100 @default.
• W2070710294 hasConceptScore W2070710294C121332964 @default.
• W2070710294 hasConceptScore W2070710294C126322002 @default.
• W2070710294 hasConceptScore W2070710294C143998085 @default.
• W2070710294 hasConceptScore W2070710294C203014093 @default.
• W2070710294 hasConceptScore W2070710294C2779282312 @default.
• W2070710294 hasConceptScore W2070710294C2780007613 @default.
• W2070710294 hasConceptScore W2070710294C2780817109 @default.
• W2070710294 hasConceptScore W2070710294C2993296363 @default.
• W2070710294 hasConceptScore W2070710294C61797465 @default.
• W2070710294 hasConceptScore W2070710294C62520636 @default.
• W2070710294 hasConceptScore W2070710294C71924100 @default.
• W2070710294 hasIssue "3" @default.
• W2070710294 hasLocation W20707102941 @default.
• W2070710294 hasLocation W20707102942 @default.
• W2070710294 hasOpenAccess W2070710294 @default.
• W2070710294 hasPrimaryLocation W20707102941 @default.
• W2070710294 hasRelatedWork W1594834870 @default.
• W2070710294 hasRelatedWork W2032502279 @default.
• W2070710294 hasRelatedWork W2055765936 @default.
• W2070710294 hasRelatedWork W2079219534 @default.
• W2070710294 hasRelatedWork W2101221673 @default.
• W2070710294 hasRelatedWork W2494791590 @default.
• W2070710294 hasRelatedWork W2800200469 @default.
• W2070710294 hasRelatedWork W3024853279 @default.
• W2070710294 hasRelatedWork W654103929 @default.
• W2070710294 hasRelatedWork W2407467520 @default.
• W2070710294 hasVolume "149" @default.
• W2070710294 isParatext "false" @default.
• W2070710294 isRetracted "false" @default.
• W2070710294 magId "2070710294" @default.
• W2070710294 workType "article" @default.