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Article ; Online: Biology and Molecular Pathogenesis of Mature T-Cell Lymphomas.

Cortés, José R / Palomero, Teresa

Cold Spring Harbor perspectives in medicine

2021 Volume 11, Issue 5

Abstract: Peripheral T-cell lymphomas (PTCLs) constitute a highly heterogeneous group of hematological diseases with complex clinical and molecular features consistent with the diversity of the T-cell type from which they originate. In the past several years, the ... ...

Abstract	Peripheral T-cell lymphomas (PTCLs) constitute a highly heterogeneous group of hematological diseases with complex clinical and molecular features consistent with the diversity of the T-cell type from which they originate. In the past several years, the systematic implementation of high-throughput genomic technologies for the analysis of T-cell malignancies has supported an exponential progress in our understanding of the genetic drivers of oncogenesis and unraveled the molecular complexity of these diseases. Recent findings have helped redefine the classification of T-cell malignancies and provided novel biomarkers to improve diagnosis accuracy and analyze the response to therapy. In addition, multiple novel targeted therapies including small-molecule inhibitors, antibody-based approaches, and immunotherapy have shown promising results in early clinical analysis and have the potential to completely change the way T-cell malignancies have been treated traditionally.
MeSH term(s)	Biomarkers ; Cell Transformation, Neoplastic/pathology ; Humans ; Lymphoma, T-Cell, Peripheral/genetics ; Lymphoma, T-Cell, Peripheral/pathology
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-05-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ISSN	2157-1422
ISSN (online)	2157-1422
DOI	10.1101/cshperspect.a035402
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Article ; Online: Targeted cellular immunotherapy for T cell malignancies.

Palomero, Teresa / Ferrando, Adolfo

Nature medicine

2017 Volume 23, Issue 12, Page(s) 1402–1403

MeSH term(s)	Humans ; Immunotherapy ; Neoplasms ; Receptors, Antigen, T-Cell, alpha-beta ; T-Lymphocytes
Chemical Substances	Receptors, Antigen, T-Cell, alpha-beta
Language	English
Publishing date	2017-12-07
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/nm.4458
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Romidepsin and Afatinib Abrogate Jak-Signal Transducer and Activator of Transcription Signaling and Elicit Synergistic Antitumor Effects in Cutaneous T-Cell Lymphoma.

Shih, Bobby B / Ma, Cindy / Cortes, Jose R / Reglero, Clara / Miller, Hannah / Quinn, S Aidan / Albero, Robert / Laurent, Anouchka P / Mackey, Adam / Ferrando, Adolfo A / Geskin, Larisa / Palomero, Teresa

The Journal of investigative dermatology

2024

Abstract: Cutaneous T-cell lymphomas are mature lymphoid neoplasias resulting from the malignant transformation of skin-resident T-cells. A distinctive clinical feature of cutaneous T-cell lymphomas is their sensitivity to treatment with histone deacetylase ... ...

Abstract	Cutaneous T-cell lymphomas are mature lymphoid neoplasias resulting from the malignant transformation of skin-resident T-cells. A distinctive clinical feature of cutaneous T-cell lymphomas is their sensitivity to treatment with histone deacetylase inhibitors. However, responses to histone deacetylase inhibitor therapy are universally transient and noncurative, highlighting the need for effective and durable drug combinations. In this study, we demonstrate that the combination of romidepsin, a selective class I histone deacetylase inhibitor, with afatinib, an EGFR family inhibitor, induces strongly synergistic antitumor effects in cutaneous T-cell lymphoma models in vitro and in vivo through abrogation of Jak-signal transducer and activator of transcription signaling. These results support a previously unrecognized potential role for histone deacetylase inhibitor plus afatinib combination in the treatment of cutaneous T-cell lymphomas.
Language	English
Publishing date	2024-01-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2023.12.010
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Article ; Online: Epidemiology of pseudomembranous conjunctivitis in a tertiary hospital: A 2-year retrospective study.

de-Arriba-Palomero, Fernando / Salvá-Palomeque, Teresa / de-Arriba-Palomero, Pablo / Arnalich-Montiel, Francisco

European journal of ophthalmology

2020 Volume 31, Issue 5, Page(s) 2275–2279

Abstract: Purpose: To describe the incidence, duration, and complication rate of patients with a clinical diagnosis of pseudomembranous viral conjunctivitis.: Methods: A retrospective observational study is performed compiling the data of patients diagnosed as ...

Abstract	Purpose: To describe the incidence, duration, and complication rate of patients with a clinical diagnosis of pseudomembranous viral conjunctivitis. Methods: A retrospective observational study is performed compiling the data of patients diagnosed as pseudomembranous conjunctivitis at the hospital's emergency department from June 2016 to May 2018. Demographic variables, duration of symptoms, and follow-up until resolution of the pseudomembranes and associated complications are collected. Results: The incidence rate of pseudomembranous conjunctivitis is 3.47/10,000 people-year and 0.123% of emergency department consultations. The incidence of pseudomembranous conjunctivitis is approximately 20% of the total adenoviral conjunctivitis, with similar peak incidence rates and annual distribution. The presence of pseudomembranes shows a mean duration of 7.86 days. In this series of pseudomembranous patients, 38.4% had at least one of the following complications: 16.7% subepithelial infiltrates (IC 13.0%-21.1%), 20.81% corneal erosions (SE 0.0218, IC 16.7%-25.5%), 3.5% filamentary keratitis (SE 0.010, IC 1.8%-6.0%), and 6.1% subtarsal fibrosis (SE 0.128, IC 3.8%-9.1%). Conclusion: To the best of our knowledge, this is the first study to investigate the incidence and rate of complications of pseudomembranous conjunctivitis. Complications occurred in almost 4 out of 10 patients. The mean duration of the follow-up in the ED was higher in patients with any complication compared with non-complicated patients. The high complication rate makes a closely follow-up advisable, until pseudomembrane resolution, to assess possible complications and symptomatic treatment.
MeSH term(s)	Conjunctivitis/epidemiology ; Conjunctivitis, Viral ; Humans ; Keratitis ; Retrospective Studies ; Tertiary Care Centers
Language	English
Publishing date	2020-09-09
Publishing country	United States
Document type	Journal Article ; Observational Study
ZDB-ID	1089461-5
ISSN	1724-6016 ; 1120-6721
ISSN (online)	1724-6016
ISSN	1120-6721
DOI	10.1177/1120672120957581
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Article ; Online: The curious origins of angioimmunoblastic T-cell lymphoma.

Cortés, José R / Palomero, Teresa

Current opinion in hematology

2016 Volume 23, Issue 4, Page(s) 434–443

Abstract: Purpose of review: Once an obscure disease, recent studies have transformed our understanding of angioimmunoblastic T-cell lymphoma (AITL). In this review, we summarize new major advances in the genetics and biology of AITL.: Recent findings: Genome ... ...

Abstract	Purpose of review: Once an obscure disease, recent studies have transformed our understanding of angioimmunoblastic T-cell lymphoma (AITL). In this review, we summarize new major advances in the genetics and biology of AITL. Recent findings: Genome wide sequencing studies have dissected the repertoire of the genetic alterations driving AITL uncovering a highly recurrent Gly17Val somatic mutation in the small GTPase RHOA and major role for mutations in epigenetic regulators, such as TET2, DNMT3A and IDH2, and signaling factors (e.g., FYN and CD28). These findings support a multistep model of follicular T helper cell transformation in AITL and pinpoint novel candidates for the development of targeted therapies in this disease. Summary: AITL originates from follicular T helper cells and is characterized by the presence of RHOA G17V mutation together with genetic alterations in TET2, DNMT3A, and IDH2. Research efforts now focus on the elucidation of the specific roles and interplay of these genetic alterations in the pathogenesis of AITL.
MeSH term(s)	Animals ; Biomarkers, Tumor ; Epigenesis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Genomics/methods ; Humans ; Immunoblastic Lymphadenopathy/diagnosis ; Immunoblastic Lymphadenopathy/etiology ; Immunoblastic Lymphadenopathy/metabolism ; Lymphoma, T-Cell/diagnosis ; Lymphoma, T-Cell/etiology ; Lymphoma, T-Cell/metabolism ; Mutation ; Receptors, Antigen, T-Cell/metabolism ; Signal Transduction ; T-Lymphocytes, Helper-Inducer/metabolism ; T-Lymphocytes, Helper-Inducer/pathology ; Transcriptome ; rhoA GTP-Binding Protein/genetics
Chemical Substances	Biomarkers, Tumor ; Receptors, Antigen, T-Cell ; rhoA GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2016-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0000000000000261
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Zs.A 3703: Show issues

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Article ; Online: Epigenetic reversal of hematopoietic stem cell aging in Phf6-knockout mice.

Wendorff, Agnieszka A / Aidan Quinn, S / Alvarez, Silvia / Brown, Jessie A / Biswas, Mayukh / Gunning, Thomas / Palomero, Teresa / Ferrando, Adolfo A

Nature aging

2022 Volume 2, Issue 11, Page(s) 1008–1023

Abstract: Aging is characterized by an accumulation of myeloid-biased hematopoietic stem cells (HSCs) with reduced developmental potential. Genotoxic stress and epigenetic alterations have been proposed to mediate age-related HSC loss of regenerative and self- ... ...

Abstract	Aging is characterized by an accumulation of myeloid-biased hematopoietic stem cells (HSCs) with reduced developmental potential. Genotoxic stress and epigenetic alterations have been proposed to mediate age-related HSC loss of regenerative and self-renewal potential. However, the mechanisms underlying these changes remain largely unknown. Genetic inactivation of the plant homeodomain 6 (Phf6) gene, a nucleolar and chromatin-associated factor, antagonizes age-associated HSC decline. Immunophenotyping, single-cell transcriptomic analyses and transplantation assays demonstrated markedly decreased accumulation of immunophenotypically defined HSCs, reduced myeloid bias and increased hematopoietic reconstitution capacity with preservation of lymphoid differentiation potential in Phf6-knockout HSCs from old mice. Moreover, deletion of Phf6 in aged mice rejuvenated immunophenotypic, transcriptional and functional hallmarks of aged HSCs. Long-term HSCs from old Phf6-knockout mice showed epigenetic rewiring and transcriptional programs consistent with decreased genotoxic stress-induced HSC aging. These results identify Phf6 as an important epigenetic regulator of HSC aging.
MeSH term(s)	Mice ; Animals ; Mice, Knockout ; Hematopoietic Stem Cells ; Aging/genetics ; Cell Differentiation ; Epigenesis, Genetic ; Repressor Proteins/genetics
Chemical Substances	Phf6 protein, mouse ; Repressor Proteins
Language	English
Publishing date	2022-11-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2662-8465
ISSN (online)	2662-8465
DOI	10.1038/s43587-022-00304-x
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Article ; Online: Dopamine D

Rendón-Ochoa, Ernesto Alberto / Padilla-Orozco, Montserrat / Calderon, Vladimir Melesio / Avilés-Rosas, Victor Hugo / Hernández-González, Omar / Hernández-Flores, Teresa / Perez-Ramirez, María Belén / Palomero-Rivero, Marcela / Galarraga, Elvira / Bargas, José

ASN neuro

2022 Volume 14, Page(s) 17590914221102075

Abstract: Summary statement: ... ...

Abstract	Summary statement: A
MeSH term(s)	Adenosine ; Animals ; Dopamine ; Parkinsonian Disorders/drug therapy ; Pramipexole ; Receptors, Dopamine D2/physiology ; Rodentia
Chemical Substances	Receptors, Dopamine D2 ; Pramipexole (83619PEU5T) ; Adenosine (K72T3FS567) ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2022-08-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2485467-0
ISSN	1759-0914 ; 1759-0914
ISSN (online)	1759-0914
ISSN	1759-0914
DOI	10.1177/17590914221102075
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Article ; Online: Pharmacologic Inhibition of NT5C2 Reverses Genetic and Nongenetic Drivers of 6-MP Resistance in Acute Lymphoblastic Leukemia.

Reglero, Clara / Dieck, Chelsea L / Zask, Arie / Forouhar, Farhad / Laurent, Anouchka P / Lin, Wen-Hsuan W / Albero, Robert / Miller, Hannah I / Ma, Cindy / Gastier-Foster, Julie M / Loh, Mignon L / Tong, Liang / Stockwell, Brent R / Palomero, Teresa / Ferrando, Adolfo A

Cancer discovery

2022 Volume 12, Issue 11, Page(s) 2646–2665

Abstract: Low-intensity maintenance therapy with 6-mercaptopurine (6-MP) limits the occurrence of acute lymphoblastic leukemia (ALL) relapse and is central to the success of multiagent chemotherapy protocols. Activating mutations in the 5'-nucleotidase cytosolic ... ...

Abstract	Low-intensity maintenance therapy with 6-mercaptopurine (6-MP) limits the occurrence of acute lymphoblastic leukemia (ALL) relapse and is central to the success of multiagent chemotherapy protocols. Activating mutations in the 5'-nucleotidase cytosolic II (NT5C2) gene drive resistance to 6-MP in over 35% of early relapse ALL cases. Here we identify CRCD2 as a first-in-class small-molecule NT5C2 nucleotidase inhibitor broadly active against leukemias bearing highly prevalent relapse-associated mutant forms of NT5C2 in vitro and in vivo. Importantly, CRCD2 treatment also enhanced the cytotoxic activity of 6-MP in NT5C2 wild-type leukemias, leading to the identification of NT5C2 Ser502 phosphorylation as a novel NT5C2-mediated mechanism of 6-MP resistance in this disease. These results uncover an unanticipated role of nongenetic NT5C2 activation as a driver of 6-MP resistance in ALL and demonstrate the potential of NT5C2 inhibitor therapy for enhancing the efficacy of thiopurine maintenance therapy and overcoming resistance at relapse. Significance: Relapse-associated NT5C2 mutations directly contribute to relapse in ALL by driving resistance to chemotherapy with 6-MP. Pharmacologic inhibition of NT5C2 with CRCD2, a first-in-class nucleotidase inhibitor, enhances the cytotoxic effects of 6-MP and effectively reverses thiopurine resistance mediated by genetic and nongenetic mechanisms of NT5C2 activation in ALL. This article is highlighted in the In This Issue feature, p. 2483.
MeSH term(s)	Humans ; Mercaptopurine/pharmacology ; Mercaptopurine/therapeutic use ; 5'-Nucleotidase/genetics ; 5'-Nucleotidase/therapeutic use ; Drug Resistance, Neoplasm/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Antineoplastic Agents/therapeutic use ; Recurrence
Chemical Substances	Mercaptopurine (E7WED276I5) ; 5'-Nucleotidase (EC 3.1.3.5) ; Antineoplastic Agents ; NT5C2 protein, human (EC 3.1.3.5)
Language	English
Publishing date	2022-08-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2625242-9
ISSN	2159-8290 ; 2159-8274
ISSN (online)	2159-8290
ISSN	2159-8274
DOI	10.1158/2159-8290.CD-22-0010
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Article ; Online: Jak-STAT Inhibition Mediates Romidepsin and Mechlorethamine Synergism in Cutaneous T-Cell Lymphoma.

Cortes, Jose R / Patrone, Christina C / Quinn, Stuart Aidan / Gu, Yuhan / Sanchez-Martin, Marta / Mackey, Adam / Cooke, Anisha J / Shih, Bobby B / Laurent, Anouchka P / Trager, Megan H / Ferrando, Adolfo A / Geskin, Larisa J / Palomero, Teresa

The Journal of investigative dermatology

2021 Volume 141, Issue 12, Page(s) 2908–2920.e7

Abstract: Sézary syndrome is an aggressive and disseminated form of cutaneous T-cell lymphoma associated with dismal prognosis in which the histone deacetylase inhibitor romidepsin has shown remarkable activity as a single agent. However, clinical responses to ... ...

Abstract	Sézary syndrome is an aggressive and disseminated form of cutaneous T-cell lymphoma associated with dismal prognosis in which the histone deacetylase inhibitor romidepsin has shown remarkable activity as a single agent. However, clinical responses to romidepsin are typically transient, highlighting the need for more effective therapies. In this study, we show synergistic antilymphoma effects of romidepsin in combination with mechlorethamine, an alkylating agent, in cutaneous T-cell lymphoma cell lines and primary samples with strong antitumor effects in an in vivo model of Sézary syndrome. Mechanistically, gene expression profiling points to abrogation of Jak/signal transducer and activator of transcription (STAT) signaling as an important mediator of this interaction. Consistently, the combination of mechlorethamine plus romidepsin resulted in downregulation of STAT5 phosphorylation in romidepsin-sensitive cell lines and primary Sézary syndrome samples, but not in romidepsin-resistant tumors. Moreover, in further support of Jak/STAT signaling as a modulator of romidepsin activity in cutaneous T-cell lymphoma, treatment with romidepsin in combination with Jak inhibitors resulted in markedly increased therapeutic responses. Overall, these results support a role for romidepsin plus mechlorethamine in combination in the treatment of cutaneous T-cell lymphoma and uncover a previously unrecognized role for Jak/STAT signaling in the response to romidepsin and romidepsin-based combination therapies in Sézary syndrome.
MeSH term(s)	Animals ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cell Line, Tumor ; Depsipeptides/administration & dosage ; Drug Synergism ; Humans ; Janus Kinase Inhibitors/pharmacology ; Lymphoma, T-Cell, Cutaneous/drug therapy ; Mechlorethamine/administration & dosage ; Mice ; STAT Transcription Factors/antagonists & inhibitors ; STAT Transcription Factors/physiology ; Signal Transduction/drug effects ; Skin Neoplasms/drug therapy
Chemical Substances	Depsipeptides ; Janus Kinase Inhibitors ; STAT Transcription Factors ; Mechlorethamine (50D9XSG0VR) ; romidepsin (CX3T89XQBK)
Language	English
Publishing date	2021-06-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2021.04.023
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Article: Acetylcholine Neurotransmitter Receptor Densities in the Striatum of Hemiparkinsonian Rats Following Botulinum Neurotoxin-A Injection.

Mann, Teresa / Zilles, Karl / Klawitter, Felix / Cremer, Markus / Hawlitschka, Alexander / Palomero-Gallagher, Nicola / Schmitt, Oliver / Wree, Andreas

Frontiers in neuroanatomy

2018 Volume 12, Page(s) 65

Abstract: Cholinergic neurotransmission has a pivotal function in the caudate-putamen, and is highly associated with the pathophysiology of Parkinson's disease. Here, we investigated long-term changes in the densities of the muscarinic receptor subtypes ... ...

Abstract	Cholinergic neurotransmission has a pivotal function in the caudate-putamen, and is highly associated with the pathophysiology of Parkinson's disease. Here, we investigated long-term changes in the densities of the muscarinic receptor subtypes M
Language	English
Publishing date	2018-08-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452969-2
ISSN	1662-5129
ISSN	1662-5129
DOI	10.3389/fnana.2018.00065
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