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

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Bibtex

@article{99f8a96a903e4fe5bfbe3832d48c05aa,
title = "Low expression of interferon regulatory factor-1 and identification of novel exons skipping in patients with chronic myeloid leukaemia",
abstract = "Chronic 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.",
keywords = "non-isotopic RNase cleavage assay, exon skipping, interferon, IRF-1, chronic myeloid leukaemia",
author = "D Tzoanopoulos and M Speletas and K Arvanitidis and C Veiopoulou and S Kyriaki and G Thyphronitis and Paschalis Sideras and G Kartalis and K Ritis",
year = "2002",
doi = "10.1046/j.1365-2141.2002.03829.x",
language = "English",
volume = "119",
pages = "46--53",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Federation of European Neuroscience Societies and Blackwell Publishing Ltd",
number = "1",

}