# Mapping and targeting 3D regulatory elements in leukemia and lymphoma

> **NIH CA R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2026 · $917,344

## Abstract

PROJECT SUMMARY/ABSTRACT
Despite cancer being typically depicted as a genetic disease, aberrations in epigenetics and gene expression
play a determinant role in transformation and response to therapies. Derailed from their developmental paths,
malignant cells may arrest their differentiation fate and activate alternative programs. Aberrant chromatin
plasticity gives a survival advantage by expanding the repertoire of epi-clones and allowing them to react to the
immune system, environmental stress, or exogenous treatments. Investigating which genetic and epigenetic
aberrations alter chromatin homeostasis and how they shape tumor heterogeneity is thus a critical challenge to
designing effective targeted approaches and predicting disease risk. Our laboratory dedicated extensive efforts
to trying to understand the non-genetic drivers of leukemia, focusing on epigenetic modifications, long non-
coding RNAs, and the study of 3D chromatin architecture. We previously investigated changes in large 3D
structures in T-cell acute lymphoblastic leukemia (T-ALL), including chromosomal compartments (A vs B) and
topological associated domains (TADs). More recently, using H3K27ac HiChIP analysis of enhancer-promoter
interactions in T-ALL, we mapped and characterized the biological role of 3D “hubs” as DNA elements that
interact with multiple other loci. We hypothesized that hubs represent regulatory units responsible for the
transcription of key genes, serving as 'headquarters' of cell identity during development but also coordinating
the tumorigenic program and shaping therapy responses. What we propose in this application is to expand our
analysis and provide a complete characterization of 3D hub interactions in both immature T cell malignancies
(T-ALL) and mature T cell neoplasms (focusing on T cell lymphoma), creating a continuum that spans normal T
cells, their progenitors and malignant counterparts at distinct stages of differentiation. Our work will highlight
how nuclear topo

## Key facts

- **NIH application ID:** 11248036
- **Project number:** 5R01CA298153-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Iannis  Aifantis; Aristotelis  Tsirigos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** CA
- **Fiscal year:** 2026
- **Award amount:** $917,344
- **Award type:** 5
- **Project period:** 2024-12-13T00:00:00 → 2029-11-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11248036

## Citation

> US National Institutes of Health, RePORTER application 11248036, Mapping and targeting 3D regulatory elements in leukemia and lymphoma (5R01CA298153-02). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/11248036. Licensed CC0.

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