FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2582206544> ?p ?o ?g. }

• W2582206544 abstract "Abstract In our recent work, we described changes in HLA class I frequencies in AML patients with nucleophosmin (NPM) mutations. Several allelic groups were found to be depleted in patients with C-terminal NPM mutations (NPMc+), but not in patients with wild-type NPM, and these differences corresponded well to in silico prediction of NPM-derived peptides binding to HLA class I. Moreover, patients with favorable HLA type (i.e., expressing HLA alleles suitable for presentation of NPM-derived peptides) were found to have significantly better overall survival than those without suitable HLA alleles. Altogether, our results suggested that spontaneous anti-NPM immune response may prevent AML development and helps achieve durable cure. In this contribution, an extended patient cohort (N = 71 patients with all available data) was divided into four groups according to HLA type (favorable/unfavorable) and Flt3-ITD status. Patients expressing suitable HLA alleles and not having internal tandem duplications in Flt3 gene (HLA+/Flt3-) had the best overall survival (Figure 1). The impact of unfavorable HLA type alone was comparable to that of Flt3-ITD positivity while the combination of both adverse factors was associated with particularly poor outcome (p = 0.0066 for trend). On the basis of these results, we believe that NPMc+ AML patients with favorable HLA type (about 65% of all NPMc+ AML patients) could benefit from an immunomodulatory therapy. Besides inhibitory receptors (such as PD-1, CTLA-4, TIM-3), regulatory T-cells or decreased HLA expression, reduced antigen presentation by leukemic cells belongs to possible mechanisms of immune escape. Insufficiency of molecular complexes such as the proteasome or the transport-associated protein (TAP) can result in increased presentation of Class II-associated invariant chain peptide (CLIP). Indeed, increased CLIP expression on residual leukemic blasts has recently been reported to correlate with increased relapse risk in AML. Interestingly, valproic acid used in combination with standard chemotherapy has been described to significantly decrease the relapse rate in elderly AML patients with mutated NPM (but not in other AML subgroups). This could be associated with restored antigen presentation following treatment with histonedeacetylase inhibitors. In our experiments, we observed marked reduction of CLIP expression on primary NPMc+ AML blasts following in vitro treatment with suberoylanilide hydroxamic acid (SAHA, Figure 2). Both the fraction of CLIP-positive cells (open circles) and CLIP surface density on positive cells (closed circles) were reduced. HLA class I expression was normal and was not affected by SAHA treatment. Importantly, the effect on CLIP expression occurred even at subtoxic (0.5 µM) drug concentration. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare." @default.
• W2582206544 created "2017-02-03" @default.
• W2582206544 creator A5000334325 @default.
• W2582206544 creator A5011721730 @default.
• W2582206544 creator A5020168393 @default.
• W2582206544 creator A5062207538 @default.
• W2582206544 creator A5066841197 @default.
• W2582206544 creator A5089243952 @default.
• W2582206544 date "2015-12-03" @default.
• W2582206544 modified "2023-09-27" @default.
• W2582206544 title "Immune Response in Acute Myeloid Leukemia with Mutated Nucleophosmin" @default.
• W2582206544 doi "https://doi.org/10.1182/blood.v126.23.2572.2572" @default.
• W2582206544 hasPublicationYear "2015" @default.
• W2582206544 type Work @default.
• W2582206544 sameAs 2582206544 @default.
• W2582206544 citedByCount "0" @default.
• W2582206544 crossrefType "journal-article" @default.
• W2582206544 hasAuthorship W2582206544A5000334325 @default.
• W2582206544 hasAuthorship W2582206544A5011721730 @default.
• W2582206544 hasAuthorship W2582206544A5020168393 @default.
• W2582206544 hasAuthorship W2582206544A5062207538 @default.
• W2582206544 hasAuthorship W2582206544A5066841197 @default.
• W2582206544 hasAuthorship W2582206544A5089243952 @default.
• W2582206544 hasConcept C104317684 @default.
• W2582206544 hasConcept C147483822 @default.
• W2582206544 hasConcept C180754005 @default.
• W2582206544 hasConcept C188280979 @default.
• W2582206544 hasConcept C203014093 @default.
• W2582206544 hasConcept C2778729363 @default.
• W2582206544 hasConcept C2779282312 @default.
• W2582206544 hasConcept C2908722627 @default.
• W2582206544 hasConcept C54355233 @default.
• W2582206544 hasConcept C71924100 @default.
• W2582206544 hasConcept C86803240 @default.
• W2582206544 hasConcept C8891405 @default.
• W2582206544 hasConceptScore W2582206544C104317684 @default.
• W2582206544 hasConceptScore W2582206544C147483822 @default.
• W2582206544 hasConceptScore W2582206544C180754005 @default.
• W2582206544 hasConceptScore W2582206544C188280979 @default.
• W2582206544 hasConceptScore W2582206544C203014093 @default.
• W2582206544 hasConceptScore W2582206544C2778729363 @default.
• W2582206544 hasConceptScore W2582206544C2779282312 @default.
• W2582206544 hasConceptScore W2582206544C2908722627 @default.
• W2582206544 hasConceptScore W2582206544C54355233 @default.
• W2582206544 hasConceptScore W2582206544C71924100 @default.
• W2582206544 hasConceptScore W2582206544C86803240 @default.
• W2582206544 hasConceptScore W2582206544C8891405 @default.
• W2582206544 hasLocation W25822065441 @default.
• W2582206544 hasOpenAccess W2582206544 @default.
• W2582206544 hasPrimaryLocation W25822065441 @default.
• W2582206544 hasRelatedWork W1982543752 @default.
• W2582206544 hasRelatedWork W2015102085 @default.
• W2582206544 hasRelatedWork W2401763117 @default.
• W2582206544 hasRelatedWork W2412240007 @default.
• W2582206544 hasRelatedWork W2468444841 @default.
• W2582206544 hasRelatedWork W2508047942 @default.
• W2582206544 hasRelatedWork W2553669774 @default.
• W2582206544 hasRelatedWork W2560455909 @default.
• W2582206544 hasRelatedWork W2566882457 @default.
• W2582206544 hasRelatedWork W2597055898 @default.
• W2582206544 hasRelatedWork W2613156114 @default.
• W2582206544 hasRelatedWork W2889475360 @default.
• W2582206544 hasRelatedWork W2948266360 @default.
• W2582206544 hasRelatedWork W2954357905 @default.
• W2582206544 hasRelatedWork W2979500677 @default.
• W2582206544 hasRelatedWork W2979592515 @default.
• W2582206544 hasRelatedWork W2995300374 @default.
• W2582206544 hasRelatedWork W3023443396 @default.
• W2582206544 hasRelatedWork W3196730579 @default.
• W2582206544 hasRelatedWork W94440457 @default.
• W2582206544 isParatext "false" @default.
• W2582206544 isRetracted "false" @default.
• W2582206544 magId "2582206544" @default.
• W2582206544 workType "article" @default.