FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2916148454> ?p ?o ?g. }

• W2916148454 endingPage "2745" @default.
• W2916148454 startingPage "2745" @default.
• W2916148454 abstract "Abstract Validated therapies for older pts with AML could rely on intensive or low-intensity strategies. Patient selection for these options remains controversial. There is currently no validated biomarker which can been used to guide therapeutic decision. TP53 mutations which are known to negatively impact AML pts outcome when treated with ICT, have been recently described as a positive prognosis factor for blast clearance with a 10-days regimen of decitabine (Welch, NEJM 2016). To date, it remains unclear whether AML pts with TP53 mutation represent a clinically homogeneous group. Several classification systems of p53 mutant, derived from in vitro or in vivo data, have been validated in solid tumors and aggressive lymphomas as predictors of p53 mutant functional impact or patient outcome. We retrospectively evaluated the impact of TP53 mutational status on the outcome of a real-world cohort of pts, treated frontline with standard doses of azacitidine (AZA). We further hypothesized that functional characterization of TP53 mutations could define a subgroup of pts with specific outcome with AZA From Jan 2007 to Dec 2016, we identified 279 AML pts enrolled in the regional cancer network ONCOMIP registry, treated frontline with AZA. Median age was 76 yrs (45-93), karyotype was adverse in 135 pts (49.1%), including 54 pts with -17 or del17p (19.4%). AML was secondary to MDS in 71 pts (25.4%), to MPN in 24 (8.6%) and therapy related in 46 pts (16.5%). Pts received a median of 6 cycles (1-67). Overall, 54 pts obtained CR/CRi (19.4%) and median OS was 10.6 months (95%CI ,9.7-12.1). For 224 pts with an available bone marrow baseline DNA sample, TP53 mutations were screened with next-generation sequencing on an Illumina® MiSeq sequencer. Sequencing results were filtered with the IARC TP53 mutations database and a variant allele frequency (VAF) >10%, strengthening the specificity of the data of this cohort. Of the 224 analyzed cases, 55 cases (24.6%) contained TP53 mutations. Response rates did not significantly differ between TP53mut (21.8% CR/CRi) and TP53wt (17.8% CR/CRi, p=.50) nor between pts with TP53mut and/or -17/del17p (19.1% CR/CRi) and pts without TP53 abnormality (18.6%CR/CRi, p=.93). Median OS was 7.9 months in pts with TP53mut and 12.6 months in TP53wt (p<.0001). With regards to the group of 109 pts with adverse karyotype, response rates did not significantly differ between TP53mut pts (20.8% CR/CRi) and TP53wt (14.3%, p=.37) and median OS was 7.9 months for TP53mut pts versus 9.6 for TP53wt pts (p=.02) Among the 55 pts with TP53mut, 53pts had adverse cytogenetics (96.4%), 16 pts had secondary AML to MDS or MPN (29.1%) and 13 had t-AML (23.6%). This subgroup included 49 cases (89%) with single TP53 mutation (missense n=42, nonsense n= 3, frameshift n=4) and 6 cases (11%) with 2 mutations (2 pts with missense and frameshift mutations and 4 pts with 2 missense mutation). We further characterized TP53mut pts with 3 validated classification systems. Due to dominant negative effect of TP53 mutation, for pts with >1 TP53 mutation, we selected the mutation with the predicted highest impact: 15 pts had disruptive mutations (i.e. missense mutation in L2/L3 helix of the DNA binding domain or truncating mutation) versus 40 pts with non-disruptive mutations (Poeta M, NEJM 2007), which was not associated with clinical response (25% in CR/CRi vs 27.9% in failure; p=1.00) nor with 6mOS (46.7% vs 55%, respectively; p=.79)Mutant p53 transactivation activity assessed with a 0-100 evolutionary score (Neskey D, Cancer Research 2015), was not associated with response (median score of 79.3[28-90] in CR/CRi vs 73.3 [49-96] in failure, p=1.00) nor with OS (HR 1.01; 95% CI, 0.99-1.03, p=.51).Relative fitness score (on a log2 scale) which was recently reported as a proxy of p53 mutant in vitro and in vivo cell proliferation advantage (Kotler E, Molecular cell 2018) was not associated with response (median score in CR/CRi of 0.094 [-0.79-0.58] vs 0.094 [-2.52-0.84] in failure, p=.68) nor with OS (HR 0.75; 95% CI, 0.45-1.22, p=.24) Overall, the response rate was not influenced by the TP53mut status, but median OS was negatively impacted by the TP53mut status in the entire cohort and in the sub-group of pts with adverse karyotype. None of the mutant p53 classification systems validated in other neoplasms succeed in identifying a subset of AML pts who specifically benefit from AZA suggesting a rather homogenous functional impact of TP53 mutations in this setting Disclosures Fornecker: Takeda: Honoraria; Servier: Honoraria." @default.
• W2916148454 created "2019-03-02" @default.
• W2916148454 creator A5001526009 @default.
• W2916148454 creator A5003424696 @default.
• W2916148454 creator A5009884108 @default.
• W2916148454 creator A5010990164 @default.
• W2916148454 creator A5011158086 @default.
• W2916148454 creator A5023048767 @default.
• W2916148454 creator A5023945751 @default.
• W2916148454 creator A5031969657 @default.
• W2916148454 creator A5037378188 @default.
• W2916148454 creator A5044999679 @default.
• W2916148454 creator A5056918871 @default.
• W2916148454 creator A5063206095 @default.
• W2916148454 creator A5065478008 @default.
• W2916148454 creator A5072312137 @default.
• W2916148454 creator A5074161015 @default.
• W2916148454 creator A5091375241 @default.
• W2916148454 date "2018-11-29" @default.
• W2916148454 modified "2023-09-27" @default.
• W2916148454 title "TP53 Mutations Negatively Impact Survival of Acute Myeloid Leukemia Patients Treated with Standard Doses of Azacitidine" @default.
• W2916148454 doi "https://doi.org/10.1182/blood-2018-99-117219" @default.
• W2916148454 hasPublicationYear "2018" @default.
• W2916148454 type Work @default.
• W2916148454 sameAs 2916148454 @default.
• W2916148454 citedByCount "0" @default.
• W2916148454 crossrefType "journal-article" @default.
• W2916148454 hasAuthorship W2916148454A5001526009 @default.
• W2916148454 hasAuthorship W2916148454A5003424696 @default.
• W2916148454 hasAuthorship W2916148454A5009884108 @default.
• W2916148454 hasAuthorship W2916148454A5010990164 @default.
• W2916148454 hasAuthorship W2916148454A5011158086 @default.
• W2916148454 hasAuthorship W2916148454A5023048767 @default.
• W2916148454 hasAuthorship W2916148454A5023945751 @default.
• W2916148454 hasAuthorship W2916148454A5031969657 @default.
• W2916148454 hasAuthorship W2916148454A5037378188 @default.
• W2916148454 hasAuthorship W2916148454A5044999679 @default.
• W2916148454 hasAuthorship W2916148454A5056918871 @default.
• W2916148454 hasAuthorship W2916148454A5063206095 @default.
• W2916148454 hasAuthorship W2916148454A5065478008 @default.
• W2916148454 hasAuthorship W2916148454A5072312137 @default.
• W2916148454 hasAuthorship W2916148454A5074161015 @default.
• W2916148454 hasAuthorship W2916148454A5091375241 @default.
• W2916148454 hasBestOaLocation W29161484541 @default.
• W2916148454 hasConcept C104317684 @default.
• W2916148454 hasConcept C126322002 @default.
• W2916148454 hasConcept C143998085 @default.
• W2916148454 hasConcept C150194340 @default.
• W2916148454 hasConcept C185592680 @default.
• W2916148454 hasConcept C190727270 @default.
• W2916148454 hasConcept C2776239401 @default.
• W2916148454 hasConcept C2778729363 @default.
• W2916148454 hasConcept C2780235182 @default.
• W2916148454 hasConcept C2781413609 @default.
• W2916148454 hasConcept C55493867 @default.
• W2916148454 hasConcept C71924100 @default.
• W2916148454 hasConcept C72563966 @default.
• W2916148454 hasConceptScore W2916148454C104317684 @default.
• W2916148454 hasConceptScore W2916148454C126322002 @default.
• W2916148454 hasConceptScore W2916148454C143998085 @default.
• W2916148454 hasConceptScore W2916148454C150194340 @default.
• W2916148454 hasConceptScore W2916148454C185592680 @default.
• W2916148454 hasConceptScore W2916148454C190727270 @default.
• W2916148454 hasConceptScore W2916148454C2776239401 @default.
• W2916148454 hasConceptScore W2916148454C2778729363 @default.
• W2916148454 hasConceptScore W2916148454C2780235182 @default.
• W2916148454 hasConceptScore W2916148454C2781413609 @default.
• W2916148454 hasConceptScore W2916148454C55493867 @default.
• W2916148454 hasConceptScore W2916148454C71924100 @default.
• W2916148454 hasConceptScore W2916148454C72563966 @default.
• W2916148454 hasIssue "Supplement 1" @default.
• W2916148454 hasLocation W29161484541 @default.
• W2916148454 hasOpenAccess W2916148454 @default.
• W2916148454 hasPrimaryLocation W29161484541 @default.
• W2916148454 hasRelatedWork W2007153145 @default.
• W2916148454 hasRelatedWork W2054507167 @default.
• W2916148454 hasRelatedWork W2167485228 @default.
• W2916148454 hasRelatedWork W2171892885 @default.
• W2916148454 hasRelatedWork W2319910057 @default.
• W2916148454 hasRelatedWork W2750605634 @default.
• W2916148454 hasRelatedWork W2889423049 @default.
• W2916148454 hasRelatedWork W4220981828 @default.
• W2916148454 hasRelatedWork W4286817035 @default.
• W2916148454 hasRelatedWork W4288066513 @default.
• W2916148454 hasVolume "132" @default.
• W2916148454 isParatext "false" @default.
• W2916148454 isRetracted "false" @default.
• W2916148454 magId "2916148454" @default.
• W2916148454 workType "article" @default.