FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3126455478> ?p ?o ?g. }

• W3126455478 abstract "Abstract Background Fms-related tyrosine kinase 3 (FLT3) receptor serves as a prognostic marker and therapeutic target in acute myeloid leukemia (AML). Approximately one-third of AML patients carry mutation in FLT3, associated with unfavourable prognosis and high relapse rate. The multitargeted kinase inhibitor midostaurin (PKC412) in combination with standard chemotherapy (daunorubicin and cytarabine) was recently shown to increase overall survival of AML patients. For that reason, PKC412 has been approved for treatment of AML patients with FLT3-mutation. PKC412 synergizes with standard chemotherapy, but the mechanism involved is not fully understood and the risk of relapse is still highly problematic. Methods By utilizing the unique nature of mass cytometry for single cell multiparameter analysis, we have explored the proteomic effect and intracellular signaling response in individual leukemic cells with internal tandem duplication of FLT3 (FLT3-ITD) after midostaurin treatment in combination with daunorubicin or cytarabine. Results We have identified a synergistic inhibition of intracellular signaling proteins after PKC412 treatment in combination with daunorubicin. In contrast, cytarabine antagonized phosphorylation inhibition of PKC412. Moreover, we found elevated levels of FLT3 surface expression after cytarabine treatment. Interestingly, the surface localization of FLT3 receptor increased in vivo on the blast cell population of two AML patients during day 3 of induction therapy (daunorubicin; once/day from day 1–3 and cytarabine; twice/day from day 1–7). We found FLT3 receptor expression to correlate with intracellular cytarabine (AraC) response. AML cell line cultured with AraC with or without PKC412 had an antagonizing phosphorylation inhibition of pAKT (p = 0.042 and 0.0261, respectively) and pERK1/2 (0.0134 and 0.0096, respectively) in FLT3 high compared to FLT3 low expressing cell populations. Conclusions Our study provides insights into how conventional chemotherapy affects protein phosphorylation of vital signaling proteins in human leukemia cells. The results presented here support further investigation of novel strategies to treat FLT3-mutated AML patients with PKC412 in combination with chemotherapy agents and the potential development of novel treatment strategies." @default.
• W3126455478 created "2021-02-15" @default.
• W3126455478 creator A5015250478 @default.
• W3126455478 creator A5020368113 @default.
• W3126455478 creator A5024467832 @default.
• W3126455478 creator A5024496530 @default.
• W3126455478 creator A5045470954 @default.
• W3126455478 creator A5045765874 @default.
• W3126455478 creator A5052423000 @default.
• W3126455478 date "2021-02-02" @default.
• W3126455478 modified "2023-10-16" @default.
• W3126455478 title "Multiplexed single‐cell mass cytometry reveals distinct inhibitory effects on intracellular phosphoproteins by midostaurin in combination with chemotherapy in AML cells" @default.
• W3126455478 cites W1980814049 @default.
• W3126455478 cites W1981811959 @default.
• W3126455478 cites W1993300766 @default.
• W3126455478 cites W2010510798 @default.
• W3126455478 cites W2015183783 @default.
• W3126455478 cites W2036161897 @default.
• W3126455478 cites W2056465113 @default.
• W3126455478 cites W2062012261 @default.
• W3126455478 cites W2100772783 @default.
• W3126455478 cites W2110808396 @default.
• W3126455478 cites W2112998845 @default.
• W3126455478 cites W2116858301 @default.
• W3126455478 cites W2125877707 @default.
• W3126455478 cites W2129615499 @default.
• W3126455478 cites W2132693111 @default.
• W3126455478 cites W2153345005 @default.
• W3126455478 cites W2170839629 @default.
• W3126455478 cites W2431218506 @default.
• W3126455478 cites W2507166450 @default.
• W3126455478 cites W2559537906 @default.
• W3126455478 cites W2605757478 @default.
• W3126455478 cites W2620184199 @default.
• W3126455478 cites W2715749014 @default.
• W3126455478 cites W2755246428 @default.
• W3126455478 cites W2909346948 @default.
• W3126455478 cites W2934924938 @default.
• W3126455478 cites W2961401803 @default.
• W3126455478 cites W2972342322 @default.
• W3126455478 cites W3000653492 @default.
• W3126455478 cites W3002123963 @default.
• W3126455478 cites W3033124631 @default.
• W3126455478 cites W3036293826 @default.
• W3126455478 cites W4231346141 @default.
• W3126455478 doi "https://doi.org/10.1186/s40164-021-00201-w" @default.
• W3126455478 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7852110" @default.
• W3126455478 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33531064" @default.
• W3126455478 hasPublicationYear "2021" @default.
• W3126455478 type Work @default.
• W3126455478 sameAs 3126455478 @default.
• W3126455478 citedByCount "4" @default.
• W3126455478 countsByYear W31264554782022 @default.
• W3126455478 countsByYear W31264554782023 @default.
• W3126455478 crossrefType "journal-article" @default.
• W3126455478 hasAuthorship W3126455478A5015250478 @default.
• W3126455478 hasAuthorship W3126455478A5020368113 @default.
• W3126455478 hasAuthorship W3126455478A5024467832 @default.
• W3126455478 hasAuthorship W3126455478A5024496530 @default.
• W3126455478 hasAuthorship W3126455478A5045470954 @default.
• W3126455478 hasAuthorship W3126455478A5045765874 @default.
• W3126455478 hasAuthorship W3126455478A5052423000 @default.
• W3126455478 hasBestOaLocation W31264554781 @default.
• W3126455478 hasConcept C104317684 @default.
• W3126455478 hasConcept C126322002 @default.
• W3126455478 hasConcept C170493617 @default.
• W3126455478 hasConcept C2776481607 @default.
• W3126455478 hasConcept C2778041864 @default.
• W3126455478 hasConcept C2778461978 @default.
• W3126455478 hasConcept C2778729363 @default.
• W3126455478 hasConcept C2781021840 @default.
• W3126455478 hasConcept C2908647359 @default.
• W3126455478 hasConcept C2910954276 @default.
• W3126455478 hasConcept C42362537 @default.
• W3126455478 hasConcept C501734568 @default.
• W3126455478 hasConcept C502942594 @default.
• W3126455478 hasConcept C55493867 @default.
• W3126455478 hasConcept C71924100 @default.
• W3126455478 hasConcept C86803240 @default.
• W3126455478 hasConcept C98274493 @default.
• W3126455478 hasConcept C99454951 @default.
• W3126455478 hasConceptScore W3126455478C104317684 @default.
• W3126455478 hasConceptScore W3126455478C126322002 @default.
• W3126455478 hasConceptScore W3126455478C170493617 @default.
• W3126455478 hasConceptScore W3126455478C2776481607 @default.
• W3126455478 hasConceptScore W3126455478C2778041864 @default.
• W3126455478 hasConceptScore W3126455478C2778461978 @default.
• W3126455478 hasConceptScore W3126455478C2778729363 @default.
• W3126455478 hasConceptScore W3126455478C2781021840 @default.
• W3126455478 hasConceptScore W3126455478C2908647359 @default.
• W3126455478 hasConceptScore W3126455478C2910954276 @default.
• W3126455478 hasConceptScore W3126455478C42362537 @default.
• W3126455478 hasConceptScore W3126455478C501734568 @default.
• W3126455478 hasConceptScore W3126455478C502942594 @default.
• W3126455478 hasConceptScore W3126455478C55493867 @default.
• W3126455478 hasConceptScore W3126455478C71924100 @default.
• W3126455478 hasConceptScore W3126455478C86803240 @default.
• W3126455478 hasConceptScore W3126455478C98274493 @default.
• W3126455478 hasConceptScore W3126455478C99454951 @default.
• W3126455478 hasFunder F4320321491 @default.

• next