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

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Low expression of interferon regulatory factor-1 and identification of novel exons skipping in patients with chronic myeloid leukaemia. / Tzoanopoulos, D; Speletas, M; Arvanitidis, K; Veiopoulou, C; Kyriaki, S; Thyphronitis, G; Sideras, Paschalis; Kartalis, G; Ritis, K.

In: British Journal of Haematology, Vol. 119, No. 1, 2002, p. 46-53.

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Tzoanopoulos, D, Speletas, M, Arvanitidis, K, Veiopoulou, C, Kyriaki, S, Thyphronitis, G, Sideras, P, Kartalis, G & Ritis, K 2002, 'Low expression of interferon regulatory factor-1 and identification of novel exons skipping in patients with chronic myeloid leukaemia', British Journal of Haematology, vol. 119, no. 1, pp. 46-53. https://doi.org/10.1046/j.1365-2141.2002.03829.x

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Tzoanopoulos, D ; Speletas, M ; Arvanitidis, K ; Veiopoulou, C ; Kyriaki, S ; Thyphronitis, G ; Sideras, Paschalis ; Kartalis, G ; Ritis, K. / Low expression of interferon regulatory factor-1 and identification of novel exons skipping in patients with chronic myeloid leukaemia. In: British Journal of Haematology. 2002 ; Vol. 119, No. 1. pp. 46-53.

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TY - JOUR

T1 - Low expression of interferon regulatory factor-1 and identification of novel exons skipping in patients with chronic myeloid leukaemia

AU - Tzoanopoulos, D

AU - Speletas, M

AU - Arvanitidis, K

AU - Veiopoulou, C

AU - Kyriaki, S

AU - Thyphronitis, G

AU - Sideras, Paschalis

AU - Kartalis, G

AU - Ritis, K

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - non-isotopic RNase cleavage assay

KW - exon skipping

KW - interferon

KW - IRF-1

KW - chronic myeloid leukaemia

U2 - 10.1046/j.1365-2141.2002.03829.x

DO - 10.1046/j.1365-2141.2002.03829.x

M3 - Article

VL - 119

SP - 46

EP - 53

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 1

ER -