SOX11 Inhibitors Are Cytotoxic in Mantle Cell Lymphoma.


Journal

Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500

Informations de publication

Date de publication:
15 08 2021
Historique:
received: 07 01 2021
revised: 19 03 2021
accepted: 27 05 2021
pubmed: 24 6 2021
medline: 2 4 2022
entrez: 23 6 2021
Statut: ppublish

Résumé

Mantle cell lymphoma (MCL) is a fatal subtype of non-Hodgkin lymphoma. SOX11 transcription factor is overexpressed in the majority of nodal MCL. We have previously reported that B cell-specific overexpression of SOX11 promotes MCL pathogenesis via critically increasing BCR signaling Using a combination of We find mechanistic validation of on-target activity of these SOX11i in the inhibition of BCR signaling and the transcriptional modulation of SOX11 target genes, specifically, in SOX11-expressing MCL cells. One of the three SOX11i exhibits relatively superior Taken together, our results provide a foundation for therapeutically targeting SOX11 in MCL by a novel class of small molecules.

Identifiants

pubmed: 34158358
pii: 1078-0432.CCR-20-5039
doi: 10.1158/1078-0432.CCR-20-5039
pmc: PMC8364871
mid: NIHMS1714578
doi:

Substances chimiques

SOX11 protein, human 0
SOXC Transcription Factors 0
Sox11 protein, mouse 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

4652-4663

Subventions

Organisme : NIGMS NIH HHS
ID : T32 GM062754
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA169487
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA244899
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA252222
Pays : United States
Organisme : NIH HHS
ID : S10 OD018522
Pays : United States
Organisme : NIH HHS
ID : S10 OD026880
Pays : United States

Informations de copyright

©2021 American Association for Cancer Research.

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Auteurs

Shashidhar S Jatiani (SS)

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

Stephanie Christie (S)

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

Violetta V Leshchenko (VV)

Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

Rinku Jain (R)

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

Abhijeet Kapoor (A)

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

Paola Bisignano (P)

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

Clement Lee (C)

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

H Ümit Kaniskan (HÜ)

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York.

Donna Edwards (D)

Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

Fanye Meng (F)

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

Alessandro Laganà (A)

Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, New York.

Youssef Youssef (Y)

Department of Internal Medicine, The Ohio State University, Columbus, Ohio.

Adrian Wiestner (A)

Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland.

Lapo Alinari (L)

Department of Internal Medicine, The Ohio State University, Columbus, Ohio.

Jian Jin (J)

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Mount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York.
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

Marta Filizola (M)

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

Aneel K Aggarwal (AK)

Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

Samir Parekh (S)

Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York. samir.parekh@mssm.edu.
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.

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Classifications MeSH