Cross talk between Wnt/β-catenin and <i>Irf8</i> in leukemia progression and drug resistance

Scheller, Marina; Schönheit, Jörg; Zimmermann, Karin; Leser, Ulf; Rosenbauer, Frank; Leutz, Achim

doi:10.1084/jem.20130706

Cited by 46 publications

(46 citation statements)

References 82 publications

(159 reference statements)

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“…Hence, IRF8 loss is a prerequisite, but not sufficient for malignant transformation, and requires additional genetic and/or environmental cues. Recently, cross talk between β-catenin and IRF8 was identified [68]. Preleukemic myeloproliferation in Irf8 −/− mice requires β-catenin, whereas a genetic alteration causing constitutive β-catenin activation in Irf8 −/− mice leads to the progression to blast crisis.…”

Section: As Already Mentioned Irf8mentioning

confidence: 99%

“…Preleukemic myeloproliferation in Irf8 −/− mice requires β-catenin, whereas a genetic alteration causing constitutive β-catenin activation in Irf8 −/− mice leads to the progression to blast crisis. Interestingly, activated β-catenin induces Irf8 expression [52,68], whereas IRF8 downregulates β-catenin expression [68,69], suggesting that IRF8 is a roadblock for β-catenin-driven leukemogenesis [68]. Importantly, BCR-ABL activates Wnt/β-catenin signaling and inhibits IRF8 expression.…”

Section: As Already Mentioned Irf8mentioning

confidence: 99%

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Regulation of myelopoiesis by the transcription factor IRF8

2015

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Section: As Already Mentioned Irf8mentioning

confidence: 99%

Section: As Already Mentioned Irf8mentioning

confidence: 99%

Regulation of myelopoiesis by the transcription factor IRF8

2015

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“…Presumably because of the lower expression level, IRF4 −/− mice, but not IRF8 −/− mice, exhibit no obvious abnormality in the development of myeloid cells compared with their wild-type controls (Yamamoto et al, 2011). Additionally, IRF8 shows a potent ability to inhibit myeloid cell growth and to promote apoptosis potentially by regulating several key genes, for example Bcl2l1, Nf1 and Bax (Huang et al, 2007;Yang et al, 2011;Scheller et al, 2013). It was also reported that IRF1 stimulates cell differentiation and mediates the N-ras-induced growth suppression of myeloid cells (Passioura et al, 2005;Schmitz et al, 2007).…”

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confidence: 99%

The interferon regulatory factors as novel potential targets in the treatment of cardiovascular diseases

Zhang

Jiang

2015

British J Pharmacology

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The family of interferon regulatory factors (IRFs) consists of nine members (IRF1-IRF9) in mammals. They act as transcription factors for the interferons and thus exert essential regulatory functions in the immune system and in oncogenesis. Recent clinical and experimental studies have identified critically important roles of the IRFs in cardiovascular diseases, arising from their participation in divergent and overlapping molecular programmes beyond the immune response. Here we review the current knowledge of the regulatory effects and mechanisms of IRFs on the immune system. The role of IRFs and their potential molecular mechanisms as novel stress sensors and mediators of cardiovascular diseases are highlighted. LINKED ARTICLESThis article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi. org/10.1111/bph.2015.172.issue-23 Abbreviations ATF3, activating transcription factor 3; CBP, CREB-binding protein; cDCs, conventional dendritic cells; CLL, chronic lymphocytic leukaemia; CMPs, common myeloid progenitor cells; CREB, cAMP-responsive element-binding protein; Dock2, dedicator of cytokinesis 2; dsRNA, double-stranded RNA; ECM, extracellular matrix; ET-1, endothelin-1; GSK3β, glycogen synthase kinase 3β; GWAS, genome-wide association studies; HATs, histone acetyltransferases; HDACs, histone deacetylases; I/R, ischaemia/reperfusion; IAD, IRF-associated domain; IFN, interferon ; IGF-I, insulin-like growth factor I; iNOS, inducible NOS; IRFs, interferon regulatory factors; MAVS, mitochondrial antiviral signalling protein; MDA5, melanoma differentiation-associated gene 5; MyD88, myeloid differentiation primary-response protein 88; PCAF, p300/CBP-associated factor; pDCs, plasma cytoid dendritic cells; PRR, pattern recognition receptor; RIG-I, retinoic acid-inducible gene I; SLE, systemic lupus erythematosus; SRF, serum response factor; TAD, transcription activation domain; TBK1, TANK-binding kinase 1; TG, transgene; TIRAP, TIR domain-containing adaptor protein; TLRs, Toll-like receptors; TRAF, TNF receptor-associated factor; TRAM, TRIF-related adaptor molecule; TRIF, TIRAP-inducing IFN-β; Tyk2, tyrosine kinase 2; VSMCs, vascular smooth muscle cells Tables of Links Introduction and backgroundThe interferon regulatory factor (IRF) family was first described as transcriptional regulators of the type I interferon (IFN) system. Since 1988, when the first IRF was identified (Miyamoto et al., 1988), most studies of IRFs have focused on their functions in immunity. Abnormalities in IRFs are associated with changes in both innate and adaptive immune responses to cellular and environmental stimuli in a wide variety of pathways. Now, more recent evidence has revealed the remarkable contributions of IRFs to other diseases, such as cardiovascular diseases Jiang et al., 2014d;Zhang et al., 2014a), metabolic diseases (Eguchi et al., 2008;2011; Wang et al., 2013c,d;2014) and oncogenesis (Yanai et al., 2012). In this review, as docume...

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“…In contrast to the conflicting results in the roles of Wnt/ β-catenin signaling in normal HSCs, past studies have consistently supported its essential roles in CML, in terms of maintenance of CML LSCs (15,16), TKI resistance (17) and disease progression to blast phase CML (18,19). BCR-ABL directly stabilizes β-catenin through its kinase activity, being an essential process in CML development in mice models (15).…”

Section: Wnt/β-catenin Signaling and Its Related Factors In Hscs And mentioning

confidence: 99%

Targeting chronic myeloid leukemia stem cells: can transcriptional program be a druggable target for cancers?

Masamoto

Kurokawa

2018

Stem Cell Investig.

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Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from acquisition of constitutively active BCR-ABL protein tyrosine kinase in a hematopoietic stem cell (HSC). Though tyrosine kinase inhibitors (TKIs) have changed a fatal disease into manageable disease, most patients cannot discontinue TKI treatment due to persistence of TKI-resistant leukemia stem cells (LSCs). Much effort has been made to find out factors or pathways specifically operating in LSCs to selectively target LSCs, with some promising results at least in preclinical models. In this article, we briefly review the role of Wnt/ β-catenin signaling and its related factors in CML LSCs, especially focusing on Tcf1/Lef1 transcription factors, major effectors of Wnt/β-catenin pathway, of which transcriptional program have recently been shown to be targetable with prostaglandin E1.

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Cross talk between Wnt/β-catenin and Irf8 in leukemia progression and drug resistance

Abstract: Cross talk between Wnt and IFN signaling determines the development of CML-leukemia–initiating cells and represents a mechanism for the acquisition of resistance to Imatinib at later stages of CML.

Cited by 46 publications

References 82 publications

Regulation of myelopoiesis by the transcription factor IRF8

Regulation of myelopoiesis by the transcription factor IRF8

The interferon regulatory factors as novel potential targets in the treatment of cardiovascular diseases

Targeting chronic myeloid leukemia stem cells: can transcriptional program be a druggable target for cancers?

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