Regulation of the Interferon regulatory factor-8 (IRF-8) Tumor Suppressor Gene by the Signal Transducer and Activator of Transcription 5 (STAT5) Transcription Factor in Chronic Myeloid Leukemia

Waight, Jeremy D.; Banik, Debarati; Griffiths, Elizabeth A.; Nemeth, Michael J.; Abrams, Scott I.

doi:10.1074/jbc.m113.544320

Cited by 27 publications

(23 citation statements)

References 46 publications

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“…It was reported that suppressing IRF8 expression by BCR-ABL involves STAT5 and Irf8 promoter DNA methylation in primary CML cells and in BCR-ABL-positive cell lines [75,76]. On the other hand, in another study that used BCR-ABL-transduced mouse bone marrow progenitor cells, inhibitors of either STAT5 or DNA methylation failed to rescue Irf8 expression [74].…”

Section: As Already Mentioned Irf8mentioning

confidence: 98%

Regulation of myelopoiesis by the transcription factor IRF8

2015

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Section: As Already Mentioned Irf8mentioning

confidence: 98%

Regulation of myelopoiesis by the transcription factor IRF8

2015

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“…It is thus unexpected that loss of IRF-8 has not been observed to generate cancer in its own right in humans. IRF-8 is downregulated in CML patients [144], which occurs via the BCR-ABL1/STAT5 signalling axis [145]. Over-expression of IRF-8 produces the opposite effect-induction of apoptosis in myeloid cell lines [146].…”

Section: Irf-8: the Antithesis Of Bcr-abl1?mentioning

confidence: 99%

Natural course and biology of CML

2015

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Chronic myeloid leukaemia (CML) is a myeloproliferative disorder arising in the haemopoietic stem cell (HSC) compartment. This disease is characterised by a reciprocal t(9;22) chromosomal translocation, resulting in the formation of the Philadelphia (Ph) chromosome containing the BCR-ABL1 gene. As such, diagnosis and monitoring of disease involves detection of BCR-ABL1. It is the BCR-ABL1 protein, in particular its constitutively active tyrosine kinase activity, that forges the pathogenesis of CML. This aberrant kinase signalling activates downstream targets that reprogram the cell to cause uncontrolled proliferation and results in myeloid hyperplasia and 'indolent' symptoms of chronic phase (CP) CML. Without successful intervention, the disease will progress into blast crisis (BC), resembling an acute leukaemia. This advanced disease stage takes on an aggressive phenotype and is almost always fatal. The cell biology of CML is also centred on BCR-ABL1. The presence of BCR-ABL1 can explain virtually all the cellular features of the leukaemia (enhanced cell growth, inhibition of apoptosis, altered cell adhesion, growth factor independence, impaired genomic surveillance and differentiation). This article provides an overview of the clinical and cell biology of CML, and highlights key findings and unanswered questions essential for understanding this disease.

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“…TRIB-2 could also induce the degradation of CEBPA protein. On the other hands, CEBPA protein interaction with AML1-ETO or c-jun was also known to inhibit the function of CEBPA itself [29][30][31][32][33]. It assumed that there are many factors that regulate the CEBPA expression and its activities in myeloid differentiation process.…”

Section: Discussionmentioning

confidence: 99%

HES-1 and CEBPA mRNA in Chronic and Late Phase (accelerated and blast crisis) of Chronic Myeloid Leukemia (CML) Patients

Rahmawati¹,

Fatmawati²,

Purwanto³

et al. 2017

J Leuk

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Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder of hematopoietic , characterized by Philadelphia chromosome containing BCR-ABL fusion gene. The gene encodes protein with constitutive tyrosine kinase activity result in myeloid proliferation and leads to form an early phase of CML called chronic phase. Unsuccessful treatment will lead to progression of the disease into late phase (accelerated and blast crisis). The mechanisms involving disease progression are still poorly understood. It is assumed that additional genetic event involves in differentiation blocking of myeloid progenitor cells, such as Hes-1 overexpression and CEBPA down regulation. However, study on the expression of these genes in CML patient's samples is still limited. This study aims to measure Hes-1 and CEBPA mRNA in chronic and late phase of CML patients. The peripheral blood mRNA level of Hes-1 was measured in CML patient's sample with BCR-ABL positive both in chronic phase (n=61) and late phase (n=17) using qRT-PCR with GAPDH as internal control. Hes-1 mRNA was statistically higher (p value=0.0) in the chronic phase (mean ± SD=97.8 ± 236.6) compared to those in late phase (mean ± SD=8.5 ± 30.7). In addition, even though CEBPA expression in chronic and late phase were not statistically different (p value=0.1), those in chronic phase (mean ± SD=5.2 ± 16.0) were generally higher compared to those in late phase (mean ± SD=1.7 ± 2.4). Hes-1 expression upregulated in 70.5% of chronic phase patients and in 17.6% of late phase patients, whereas CEBPA expression down regulated in 42.6% of chronic phase patients and in 47.1% in late phase patients. High standard deviation, particularly in mRNA Hes-1 gene expression measurement of the chronic phase, indicated the presence of individual variations in the sample that might be influenced by other genetic factors. This study found that Hes-1 mRNA is significantly higher in peripheral blood of chronic phase than blast crisis CML, whereas CEBPA mRNA is not different.

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Regulation of the Interferon regulatory factor-8 (IRF-8) Tumor Suppressor Gene by the Signal Transducer and Activator of Transcription 5 (STAT5) Transcription Factor in Chronic Myeloid Leukemia

Cited by 27 publications

References 46 publications

Regulation of myelopoiesis by the transcription factor IRF8

Regulation of myelopoiesis by the transcription factor IRF8

Natural course and biology of CML

HES-1 and CEBPA mRNA in Chronic and Late Phase (accelerated and blast crisis) of Chronic Myeloid Leukemia (CML) Patients

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