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Methyltransferase inhibitors restore SATB1 protective activity against cutaneous T cell lymphoma in mice

J Clin Invest. 2020-12; 
Carly M Harro, Jairo Perez-Sanz, Tara Lee Costich, Kyle K Payne, Carmen M Anadon Galindo, Ricardo A Chaurio, Subir Biswas, Gunjan Mandal, Kristen E Rigolizzo, Kimberly B Sprenger, Jessica A Mine, Louise Showe, Xiaoqing Yu, Kebin Liu, Paulo C Rodriguez, Javier Pinilla-Ibarz, Lubomir Sokol, Jose R Conejo-Garcia
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ORF cDNA Clones/MolecularCloud … L3000001) following manufacture's recommendations with pBMN-I-GFP vector containing human SATB1 ORF (GenScript Biotech) cloned using the EcoRI and BamHI restriction sites. Virus was collected in complete medium at 48 and 72hrs and filtered through a 40uM filter … Get A Quote

摘要

Cutaneous T cell lymphoma (CTCL) has a poorly understood etiology and no cure. Using conditional knockout mice, we found that ablation of the genomic organizer Special AT-rich sequence-binding protein-1 (Satb1) caused malignant transformation of mature, skin-homing, Notch-activated CD4+ and CD8+ T-cells into progressively fatal lymphoma. Mechanistically, Satb1 restrained Stat5 phosphorylation and the expression of skin-homing chemokine receptors in mature T-cells. Notably, methyltransferase-dependent epigenetic repression of SATB1 was universally found in human Sézary syndrome, but not in other peripheral T-cell malignancies. H3K27 and H3K9 trimethylation occluded the SATB1 promoter in Sézary cells, while inh... More

关键词

Hematology, Lymphomas