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Connecting the dots in cutaneous T cell lymphoma (CTCL): STAT5 regulates malignant T cell proliferation via miR-155.

Litvinov IV, Pehr K, Sasseville D - Cell Cycle (2013)

View Article: PubMed Central - PubMed

Affiliation: Division of Dermatology; Department of Medicine; McGill University; Montreal, Quebec, Canada.

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Cutaneous T-cell lymphomas (CTCLs) are a group of lymphoproliferative disorders affecting the skin... The etiology of CTCLs is unknown, and the pathogenesis remains elusive... Early stages of CTCL mimic benign inflammatory disorders, including psoriasis and eczema, with malignant T cells homing to the skin... In the article by Kopp et al., the authors establish STAT5-mediated upregulation of mir-155 as an important step in CTCL carcinogenesis... They provide evidence that miR-155 is induced via transcription factor STAT5 through either cytokine (IL-2/IL-15)-dependent or constitutive activation in malignant and non-malignant T cells, including PBMCs and primary CTCL cells (Fig.  1)... Furthermore, they found miR-155 to be involved in malignant proliferation... Since miR-155 has also been implicated in genomic instability in cancer, it is possible that STAT5, via induction of miR-155, also drives genomic instability, a key feature of CTCL... As mentioned above, one of the major obstacles in managing CTCL is our inability to consistently achieve cure of this cancer... Due to its heterogeneity, there is no common genetic aberration or biomarker providing a reliable therapeutic target for patients... To achieve effective cure, CTCL therapy is in need of new targets and treatment strategies... Kopp et al. showed that treatment of malignant cells with JAK inhibitor tofacitinib (CP 690 550) strongly inhibits miR-155 expression and STAT5 activation... These results suggest a therapeutic potential of JAK inhibitors.

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Figure 1. STAT5 signaling trans activates miR-155 expression, which can be blocked upstream at the level of JAK kinase signaling by tofacitinib inhibitor.
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Figure 1: Figure 1. STAT5 signaling trans activates miR-155 expression, which can be blocked upstream at the level of JAK kinase signaling by tofacitinib inhibitor.

Mentions: In the article by Kopp et al., the authors establish STAT5-mediated upregulation of mir-155 as an important step in CTCL carcinogenesis.2 Indeed, microRNA (miRNA) studies only recently became a prominent part of CTCL research. Specifically, Ralfkiaer et al. identified a set of miRNA classifiers that can be employed to distinguish early stages of CTCL from other benign inflammatory conditions.3 Still, unfortunately, functional data on miRNA remains sparse and has only begun to emerge in the last few years. miR-155 was recently highlighted as being upregulated in CTCL.3 This gene is a well-studied miRNA that is crucial for inflammation and is often overexpressed in various cancers. In their seminal article Kopp et al. discovered a link between miR-155 expression and JAK/STAT signaling in CTCL.2 They provide evidence that miR-155 is induced via transcription factor STAT5 through either cytokine (IL-2/IL-15)-dependent or constitutive activation in malignant and non-malignant T cells, including PBMCs and primary CTCL cells (Fig. 1). Furthermore, they found miR-155 to be involved in malignant proliferation. Their results are intriguing, because they connect some of the major hallmarks in CTCL: an increased expression of oncomiR-155, deregulation of JAK/STAT signaling pathways, and a persistent activation of STAT transcription factors.2,4


Connecting the dots in cutaneous T cell lymphoma (CTCL): STAT5 regulates malignant T cell proliferation via miR-155.

Litvinov IV, Pehr K, Sasseville D - Cell Cycle (2013)

Figure 1. STAT5 signaling trans activates miR-155 expression, which can be blocked upstream at the level of JAK kinase signaling by tofacitinib inhibitor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3755065&req=5

Figure 1: Figure 1. STAT5 signaling trans activates miR-155 expression, which can be blocked upstream at the level of JAK kinase signaling by tofacitinib inhibitor.
Mentions: In the article by Kopp et al., the authors establish STAT5-mediated upregulation of mir-155 as an important step in CTCL carcinogenesis.2 Indeed, microRNA (miRNA) studies only recently became a prominent part of CTCL research. Specifically, Ralfkiaer et al. identified a set of miRNA classifiers that can be employed to distinguish early stages of CTCL from other benign inflammatory conditions.3 Still, unfortunately, functional data on miRNA remains sparse and has only begun to emerge in the last few years. miR-155 was recently highlighted as being upregulated in CTCL.3 This gene is a well-studied miRNA that is crucial for inflammation and is often overexpressed in various cancers. In their seminal article Kopp et al. discovered a link between miR-155 expression and JAK/STAT signaling in CTCL.2 They provide evidence that miR-155 is induced via transcription factor STAT5 through either cytokine (IL-2/IL-15)-dependent or constitutive activation in malignant and non-malignant T cells, including PBMCs and primary CTCL cells (Fig. 1). Furthermore, they found miR-155 to be involved in malignant proliferation. Their results are intriguing, because they connect some of the major hallmarks in CTCL: an increased expression of oncomiR-155, deregulation of JAK/STAT signaling pathways, and a persistent activation of STAT transcription factors.2,4

View Article: PubMed Central - PubMed

Affiliation: Division of Dermatology; Department of Medicine; McGill University; Montreal, Quebec, Canada.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Cutaneous T-cell lymphomas (CTCLs) are a group of lymphoproliferative disorders affecting the skin... The etiology of CTCLs is unknown, and the pathogenesis remains elusive... Early stages of CTCL mimic benign inflammatory disorders, including psoriasis and eczema, with malignant T cells homing to the skin... In the article by Kopp et al., the authors establish STAT5-mediated upregulation of mir-155 as an important step in CTCL carcinogenesis... They provide evidence that miR-155 is induced via transcription factor STAT5 through either cytokine (IL-2/IL-15)-dependent or constitutive activation in malignant and non-malignant T cells, including PBMCs and primary CTCL cells (Fig.  1)... Furthermore, they found miR-155 to be involved in malignant proliferation... Since miR-155 has also been implicated in genomic instability in cancer, it is possible that STAT5, via induction of miR-155, also drives genomic instability, a key feature of CTCL... As mentioned above, one of the major obstacles in managing CTCL is our inability to consistently achieve cure of this cancer... Due to its heterogeneity, there is no common genetic aberration or biomarker providing a reliable therapeutic target for patients... To achieve effective cure, CTCL therapy is in need of new targets and treatment strategies... Kopp et al. showed that treatment of malignant cells with JAK inhibitor tofacitinib (CP 690 550) strongly inhibits miR-155 expression and STAT5 activation... These results suggest a therapeutic potential of JAK inhibitors.

Show MeSH
Related in: MedlinePlus