例如:"lncRNA", "apoptosis", "WRKY"

Contribution of STAT3 and RAD23B in Primary Sézary Cells to Histone Deacetylase Inhibitor FK228 Resistance.

J. Invest. Dermatol.2019 Sep;139(9):1975-1984.e2. Epub 2019 Mar 22
Rosie M Butler 1 , Robert C McKenzie 1 , Christine L Jones 1 , Charlotte E Flanagan 1 , Wesley J Woollard 1 , Maria Demontis 1 , Silvia Ferreira 1 , Isabella Tosi 1 , Susan John 2 , Sean J Whittaker 1 , Tracey J Mitchell 3
Rosie M Butler 1 , Robert C McKenzie 1 , Christine L Jones 1 , Charlotte E Flanagan 1 , Wesley J Woollard 1 , Maria Demontis 1 , Silvia Ferreira 1 , Isabella Tosi 1 , Susan John 2 , Sean J Whittaker 1 , Tracey J Mitchell 3
+ et al

[No authors listed]

Author information
  • 1 St. John's Institute of Dermatology, King's College London, Guy's Hospital, London, UK.
  • 2 Department of Immunology, Infection and Inflammatory Disease, King's College London, Guy's Hospital, London, UK.
  • 3 St. John's Institute of Dermatology, King's College London, Guy's Hospital, London, UK. Electronic address: tracey.mitchell@kcl.ac.uk.

摘要


FK228 (romidepsin) and suberoylanilide hydroxamic acid (vorinostat) are histone deacetylase inhibitors (HDACi) approved by the US Food and Drug Administration for cutaneous T-cell lymphoma (CTCL), including the leukemic subtype Sézary syndrome. This study investigates RAD23B and gene perturbations in a large cohort of primary Sézary cells and the effect of FK228 treatment on tyrosine phosphorylation of duanyu18133 and RAD23B expression. We report RAD23B copy number variation in 10% (12/119, P ≤ 0.01) of SS patients, associated with reduced mRNA expression (P = 0.04). RAD23B knockdown in a CTCL cell line led to a reduction in FK228-induced apoptosis. Histone deacetylase inhibitor treatment significantly reduced in primary Sézary cells and was partially mediated by RAD23B. A distinct pattern of co-expression in primary Sézary cells was detected. Critically, Sézary cells harboring the common duanyu18133 Y640F variant were less sensitive to FK228-induced apoptosis and exogenous expression of duanyu18133 Y640F, and D661Y conferred partial resistance to duanyu18133 transcriptional inhibition by FK228 (P ≤ 0.0024). These findings suggest that RAD23B and duanyu18133 gene perturbations could reduce sensitivity to histone deacetylase inhibitors in SS patients.