FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1551350274> ?p ?o ?g. }

• W1551350274 abstract "Acute myeloid leukaemia (AML) is a heterogeneous clonal disorder of haematopoietic cells that primarily affects the elderly. Previously, our laboratory identified y-catenin as significantly overexpressed in AML. y-Catenin shares close structural and functional homology with the more intensively studied /3-catenin. Both catenins have dual roles in cell adhesion complexes and in transcription. Their transcriptional role is regulated by Wnt signalling which is critical for normal development and is one of the most frequently dysregulated processes in AML. In spite of this, little is known regarding the specific role of y-catenin in normal haematopoiesis or AML pathology. This study devised an intracellular flow cytometric staining assay to characterise the expression of y-catenin in normal haematopoietic subsets. y-Catenin exhibited a similar expression profile to /3-catenin. Expression was relatively high in haematopoietic stem/progenitor cells (HSC/HPC) and showed increased expression in myeloid differentiated cells (granulocytes and monocytes) while expression was lower in lymphoid cells and undetectable in red blood cells. Studies of subcellular distribution by confocal imaging showed reciprocal localisation of catenins in CD34+ cells, with /3-catenin predominantly nuclear translocated and y-catenin nuclear excluded. Conversely, in granulocytic and monocytic cells nuclear y-catenin levels were relatively high whilst nuclear /3-catenin levels were reduced. A small subset of the CD14+ monocyte population exhibited heavily nuclear translocated y-catenin. Subsequent knock-down studies of y-catenin showed this protein to be required for normal haematopoietic development in vitro, evidenced by the inhibition of macrophage differentiation and apparent reprogramming of committed monocyte progenitors for granulocytic development. In AML patients, y- catenin mRNA expression conferred a reduced complete remission rate arising from resistant disease, however discordance was found between mRNA and protein level, implying post-translational control of y-catenin expression in AML. In primary AML blasts (undifferentiated) y-catenin was aberrantly localised to the nucleus suggesting a transcriptional role in AML pathology. A correlation was identified between y- and (3-catenin protein expression in primary AML blasts and an association between nuclear levels of these proteins. To determine whether this association was causal, y-catenin was ectopically expressed in normal human CD34+ haematopoietic progenitor cells but had no significant influence on /3-catenin expression or localisation even following subsequent differentiation. In contrast, overexpression of y-catenin in leukaemic cell lines stabilised /3-catenin protein and promoted its translocation to the nucleus suggesting that the influence of y-catenin on /5-catenin is a feature of leukaemic cells but not normal cells. Phenotypically, overexpression of y-catenin had little effect on normal progenitor cells but was able to block agonist-induced differentiation of AML cell lines, probably via stabilisation of jS-catenin. In summary, this study indicates a role for y-catenin in the regulation of normal haematopoietic development and that its nuclear translocation is strictly regulated independently of /3-catenin in normal haematopoiesis. In leukaemic cells, however, this control is dysfunctional allowing y-catenin to promote the stabilisation and translocation of /3-catenin. This relationship may represent a pathological mechanism active in AML blasts to block myeloid differentiation and promote a leukaemic phenotype." @default.
• W1551350274 created "2016-06-24" @default.
• W1551350274 creator A5010617221 @default.
• W1551350274 date "2011-01-01" @default.
• W1551350274 modified "2023-09-25" @default.
• W1551350274 title "Role of γ-catenin in acute myeloid leukaemia" @default.
• W1551350274 hasPublicationYear "2011" @default.
• W1551350274 type Work @default.
• W1551350274 sameAs 1551350274 @default.
• W1551350274 citedByCount "0" @default.
• W1551350274 crossrefType "dissertation" @default.
• W1551350274 hasAuthorship W1551350274A5010617221 @default.
• W1551350274 hasConcept C10205521 @default.
• W1551350274 hasConcept C109159458 @default.
• W1551350274 hasConcept C137620995 @default.
• W1551350274 hasConcept C201750760 @default.
• W1551350274 hasConcept C2779282312 @default.
• W1551350274 hasConcept C28328180 @default.
• W1551350274 hasConcept C2908647359 @default.
• W1551350274 hasConcept C30145163 @default.
• W1551350274 hasConcept C502942594 @default.
• W1551350274 hasConcept C62478195 @default.
• W1551350274 hasConcept C71924100 @default.
• W1551350274 hasConcept C86803240 @default.
• W1551350274 hasConcept C95444343 @default.
• W1551350274 hasConcept C99454951 @default.
• W1551350274 hasConceptScore W1551350274C10205521 @default.
• W1551350274 hasConceptScore W1551350274C109159458 @default.
• W1551350274 hasConceptScore W1551350274C137620995 @default.
• W1551350274 hasConceptScore W1551350274C201750760 @default.
• W1551350274 hasConceptScore W1551350274C2779282312 @default.
• W1551350274 hasConceptScore W1551350274C28328180 @default.
• W1551350274 hasConceptScore W1551350274C2908647359 @default.
• W1551350274 hasConceptScore W1551350274C30145163 @default.
• W1551350274 hasConceptScore W1551350274C502942594 @default.
• W1551350274 hasConceptScore W1551350274C62478195 @default.
• W1551350274 hasConceptScore W1551350274C71924100 @default.
• W1551350274 hasConceptScore W1551350274C86803240 @default.
• W1551350274 hasConceptScore W1551350274C95444343 @default.
• W1551350274 hasConceptScore W1551350274C99454951 @default.
• W1551350274 hasLocation W15513502741 @default.
• W1551350274 hasOpenAccess W1551350274 @default.
• W1551350274 hasPrimaryLocation W15513502741 @default.
• W1551350274 hasRelatedWork W1644646680 @default.
• W1551350274 hasRelatedWork W1960942182 @default.
• W1551350274 hasRelatedWork W1988033413 @default.
• W1551350274 hasRelatedWork W1994441995 @default.
• W1551350274 hasRelatedWork W2031321792 @default.
• W1551350274 hasRelatedWork W2070840297 @default.
• W1551350274 hasRelatedWork W2071086080 @default.
• W1551350274 hasRelatedWork W2083193063 @default.
• W1551350274 hasRelatedWork W2092845229 @default.
• W1551350274 hasRelatedWork W2093804773 @default.
• W1551350274 hasRelatedWork W2153641896 @default.
• W1551350274 hasRelatedWork W2168289490 @default.
• W1551350274 hasRelatedWork W2182749522 @default.
• W1551350274 hasRelatedWork W2563574018 @default.
• W1551350274 hasRelatedWork W2570285428 @default.
• W1551350274 hasRelatedWork W2579597326 @default.
• W1551350274 hasRelatedWork W2920796086 @default.
• W1551350274 hasRelatedWork W3042900979 @default.
• W1551350274 hasRelatedWork W3082191411 @default.
• W1551350274 hasRelatedWork W3186424953 @default.
• W1551350274 isParatext "false" @default.
• W1551350274 isRetracted "false" @default.
• W1551350274 magId "1551350274" @default.
• W1551350274 workType "dissertation" @default.