# Regulation of TAL1/SCL in T-Cell Leukemia

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2021 · $315,103

## Abstract

Abstract:
 Aberrant activation of TAL1 oncogene is associated with up to 60% of T-cell acute lymphoblastic
leukemia (T-ALL) patients. Its ectopic expression also led to development of leukemia or lymphoma in mice. In
contrast, deletion of TAL1 in T-ALL cells lost leukemic phenotype and induced apoptosis. Furthermore, the
TAL1 expressing T-ALL subtype is associated with poor prognosis and high rate of relapse. These data
suggest that dysregulation of TAL1 oncogene plays an important role in T-ALL leukemogenesis. However, in
normal hematopoiesis, TAL1 is a hematopoietic-specific member of the basic helix-loop-helix family of
transcription factors required for self-renewal of hematopoietic stem cells and the development of all
hematopoietic lineages. Because of its relevance to normal hematopoietic differentiation and T-cell leukemia, it
is critical to know how TAL1 oncogene is differentially activated in normal hematopoietic cells and T-cell acute
leukemia. Understanding of the epigenetic mechanisms governing TAL1 transcriptional regulation will provide
a new insight into epigenetic control of hematopoiesis as well as pathogenesis of T-ALL diseases which may
lead to new strategies for leukemia diagnosis and therapeutic approaches.
 We recently found that TAL1 transcription is regulated by different intra- and interchromosomal loops in
normal hematopoietic and leukemia cells, respectively. These intra- and interchromosomal loops alter the cell-
type specific enhancers that interact with the TAL1 promoter. Based on these data, we hypothesize that
repositioning of the TAL1 gene in a close proximity with T-cell specific transcriptionally active loci within
nucleus is essential for aberrantly activating TAL1 oncogene in T-ALL. In this proposal, we will investigate the
underlying molecular mechanisms that connect chromatin loops with transcriptional activation decision of the
TAL1 oncogene as well as elucidate the role of CTCF and enhancer regulatory elements mediated chromatin
interactions in regulation of TAL1 gene during normal hematopoiesis and leukemogenesis. The specific aims
are: 1) Evaluate the role of CTCF mediated genome organization in regulation of enhancer/ promoter
interaction and TAL1 transcription during hematopoiesis and T cell leukemogenesis; 2) Study the molecular
mechanisms by which interchromosomal loops result in aberrant activation of TAL1 oncogene in T-ALL.

## Key facts

- **NIH application ID:** 10094201
- **Project number:** 5R01CA204044-05
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Suming Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $315,103
- **Award type:** 5
- **Project period:** 2017-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10094201

## Citation

> US National Institutes of Health, RePORTER application 10094201, Regulation of TAL1/SCL in T-Cell Leukemia (5R01CA204044-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10094201. Licensed CC0.

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