# Epiproteomics of Sezary Syndrome

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $610,351

## Abstract

PROJECT SUMMARY
EPIPROTEOME OF SEZARY SYNDROME
Peripheral T-cell lymphomas including cutaneous T-cell lymphomas (CTCL) are poorly understood and
many subtypes exhibit aggressive clinical course and high mortality with short (2-year) life expectancy after
diagnosis. Poor understanding of mechanisms underlying the pathogenesis of CTCLs contributes to
suboptimal diagnostic subcategorization and lack of targeted therapies. Mycosis fungoides (MF) and Sézary
syndrome (SS) are two major forms of CTCL. Clinical staging and outcome of MF and SS is dependent on
the quantity of neoplastic cells in the blood. While SS is an aggressive disease with poor overall survival
(42.3% at 5 years and is by definition diagnosed at late stage disease, there are many patients with low
tumor burden (Early-stage CTCL) who suffer from delay in diagnosis due to the subjective nature of the
diagnostic criteria. The mean diagnostic delay (measured as the time from emergence of skin lesions to the
diagnosis of SS) is long (4.2 year; median 2.8 years) with a significant variation (1 month to 32 years). The
suboptimal diagnostic accuracy and imprecision of disease detection necessitates the development
of qualitative and objective biomarkers of SS. Histone deacetylase inhibitors (HDACi) have been
introduced as anti- cancer agents which achieve their therapeutic effect in part by inhibiting deacetylation of
histones. However, despite the fact that CTCLs including SS were the first diseases which received FDA
approval for treatment with HDACi, responses to the drugs in each patient are markedly variable. An unmet
clinical need is the absence of reliable biomarkers directly interrogating the histone PTMs that can predict
response to the drugs. We recently developed a novel mass spectrometry (MS)-based strategy for unbiased
identification of histone PTMs and demonstrated its applicability for the analysis of primary samples of SS.
Importantly, these epiproteomic profiling studies reveal distinctive histone PTM marks that distinguish SS
from CD4+ T-cells from healthy individuals. It is our central hypothesis that epiproteomic modifications
(the histone code) of SS can be utilized for the early diagnosis and as predictors of response to
HDACi. Accordingly, we propose to investigate the utility of MS-based epiproteomic profiling for the early
diagnosis of SS and for the prediction of response to HDACi. The overall impact of this proposal is the
establishment of novel epiproteomic biomarkers that will improve outcomes particularly in aggressive
CTCLs.

## Key facts

- **NIH application ID:** 10031052
- **Project number:** 1R01CA251764-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** KOJO S. J. ELENITOBA-JOHNSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $610,351
- **Award type:** 1
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10031052

## Citation

> US National Institutes of Health, RePORTER application 10031052, Epiproteomics of Sezary Syndrome (1R01CA251764-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10031052. Licensed CC0.

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