Low expression of interferon regulatory factor-1 and identification of novel exons skipping in patients with chronic myeloid leukaemia

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dc.contributor.authorTzoanopoulos, D.en
dc.contributor.authorSpeletas, M.en
dc.contributor.authorArvanitidis, K.en
dc.contributor.authorVeiopoulou, C.en
dc.contributor.authorKyriaki, S.en
dc.contributor.authorThyphronitis, G.en
dc.contributor.authorSideras, P.en
dc.contributor.authorKartalis, G.en
dc.contributor.authorRitis, K.en
dc.date.accessioned2015-11-24T16:32:52Z
dc.date.available2015-11-24T16:32:52Z
dc.identifier.issn0007-1048-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/7596
dc.rightsDefault Licence-
dc.subjectirf-1en
dc.subjectchronic myeloid leukaemiaen
dc.subjectinterferonen
dc.subjectexon skippingen
dc.subjectnon-isotopic rnase cleavage assayen
dc.subjectchronic myelogenous leukemiaen
dc.subjectsequence binding-proteinen
dc.subjectcytogenetic responseen
dc.subjectfactor-ien
dc.subjecttranscription factoren
dc.subjectirf-1en
dc.subjectalphaen
dc.subjectgeneen
dc.subjectmutationen
dc.subjectcellsen
dc.titleLow expression of interferon regulatory factor-1 and identification of novel exons skipping in patients with chronic myeloid leukaemiaen
heal.abstractChronic myeloid leukaemia (CML) is a malignant clonal disorder of the haematopoietic stem cell. Treatment of CML patients with interferon alpha (IFN-alpha) has induced haematological and cytogenetic remission. Interferons transcriptionally activate target genes through the JAK-STAT and interferon regulated factors (IRFs) family pathways. Interferon regulated factor-1 (IRF-1) is a transcriptional activator of genes critical for cell growth, differentiation and apoptosis. The skipping of exons 2 or 2 and 3 of IRF-1 in patients with myelodysplastic syndromes and acute myelogenous leukaemia suggests that this factor may have a critical role in leukaemogenesis. The role of IRF-1 in CML is currently unknown. Therefore, mutational analysis of IRF-1 was performed and its expression pattern was also studied in CML patients. We studied IRF-1 in peripheral blood mononuclear cells of 21 patients in chronic phase CML. No point mutations were identified at the cDNA level. Surprisingly, fourfold reduction of full-length IRF-1 mRNA expression was established in 17/21 patients compared with normal individuals. Low expression of full-length IRF-1 was observed in conjunction with high levels of aberrantly spliced mRNAs, reported for the first time. In three patients who were also analysed during blastic transformation, further reduction of full-length IRF-1 mRNA was observed. These findings demonstrate that, in CML patients, IRF-1 can produce high levels of aberrant spliced mRNAs with subsequent reduction in the levels of full-length IRF-1 mRNA. This observation is consistent with the notion that exon skipping may constitute another mechanism of tumour suppressor gene inactivation in this disease.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondary<Go to ISI>://000178348000007-
heal.journalNameBr J Haematolen
heal.journalTypepeer reviewed-
heal.languageen-
heal.publicationDate2002-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιώνel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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