Constitutive Activation of Signal Transducers and Activators of Transcription Predicts Vorinostat Resistance in Cutaneous T-Cell Lymphoma

Fantin, Valeria R.; Loboda, Andrey; Paweletz, Cloud P.; Hendrickson, Ronald C.; Pierce, Jacqueline W.; Roth, Jennifer A.; Li, Lixia; Gooden, Frank; Korenchuk, Susan; Hou, Xiaoming; Harrington, Elizabeth A.; Randolph, Sophia; Reilly, John F.; Ware, Christopher; Kadin, Marshall E.; Frankel, Stanley R.; Richon, Victoria M.

doi:10.1158/0008-5472.can-07-6091

Cited by 161 publications

(137 citation statements)

References 49 publications

(52 reference statements)

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“…As Janus kinases such as JAK3 and JAK1 are constitutively active in malignant T cells, 30,42 we examined the effect of JAK inhibition on STAT5 activation and miR-155 expression in malignant T cell lines and primary PBMCs from a SS patient. As shown in Figure 3C and D, a selective inhibitor of JAK kinases (CP-690550) strongly inhibited the activation of STAT5 and triggered a decreased expression of miR-155, supporting the idea that STAT5 drives BIC and miR-155 expression.…”

Section: Resultsmentioning

confidence: 99%

STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma

et al. 2013

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Section: Resultsmentioning

confidence: 99%

STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma

et al. 2013

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“…JAK1 is less frequently mutated (10%) compared with JAK3 (30%) and STAT5B (36%) [70]. Indeed, studies have linked JAK3 and STAT5B mutations with poorer patient survival [83,84]. STAT5 activation was also linked to an autocrine PDGF signaling loop in PTCL-NOS [85].…”

Section: Targets In Ptcl and Driver Mutationsmentioning

confidence: 99%

“…Enhanced STAT5 signaling was also linked to overexpression of oncogenic miR-155 in CTCL [86], associated with downregulation of tumor-suppressive miR-22 [87], or enhanced disease progression caused by Lymphotoxin-α-dependent lymphangiogenesis [88]. STAT5-dependent CD80 expression was also linked to resistance to Vorinostat and risk of disease progression in PTCL [84,89,90]. …”

Section: Targets In Ptcl and Driver Mutationsmentioning

confidence: 99%

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Orlova

Wingelhofer

Neubauer

et al. 2017

Expert Opinion on Therapeutic Targets

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Introduction: Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations in chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages. We summarize how these pathways might be interconnected in normal or cancer cells, which have lost differentiation capacity and drive oncogene transcription. Expert opinion: Due to similarities in driver mutations including epigenetic enzymes, JAK-STAT pathway activation and mutated checkpoint control through TP53, we hypothesize that similar therapeutic approaches could be of benefit in these diseases. We give an overview of how driver mutations in these malignancies contribute to hematopoietic cancer initiation or progression, and how these pathways can be targeted with currently available tools.

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“…Further studies are needed to fully define the mechanisms of resistance to HDAC inhibition in CTCL [255,[279][280][281][282], enabling the development of rational therapeutic combinations incorporating HDAC inhibitors in CTCL [283,284].…”

Section: Hdac Inhibitorsmentioning

confidence: 99%

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

Wilcox

2011

American J Hematol

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Disease overview: Cutaneous T‐cell lymphomas are a heterogenous group of T‐cell lymphoproliferative disorders involving the skin, the majority of which may be classified as Mycosis fungoides (MF) or Sézary syndrome (SS).Diagnosis: The diagnosis of MF or SS requires the integration of clinical and histopathologic data.Risk‐adapted therapy: Tumor, node, metastasis, and blood (TNMB) staging remains the most important prognostic factor in MF/SS and forms the basis for a “risk‐adapted,” multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin‐directed therapies is preferred, as both disease‐specific and overall survival for these patients is favorable. In contrast, patients with advanced‐stage disease with significant nodal, visceral, or blood involvement are generally approached with biologic‐response modifiers, denileukin diftitox, and histone deacetylase inhibitors before escalating therapy to include systemic, single‐agent chemotherapy. Multiagent chemotherapy may be used for those patients with extensive visceral involvement requiring rapid disease control. In highly‐selected patients with disease refractory to standard treatments, allogeneic stem‐cell transplantation may be considered. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.

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Constitutive Activation of Signal Transducers and Activators of Transcription Predicts Vorinostat Resistance in Cutaneous T-Cell Lymphoma

Cited by 161 publications

References 49 publications

STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma

STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

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