# Sin3B’s role in coordinating cell cycle exit and differentiation in hematopoiesis - Funded Extension

> **NIH NIH F31** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $13,912

## Abstract

PROJECT SUMMARY
 Hematopoietic stem cells (HSCs) in the bone marrow must maintain a constant production of effector blood
cells to maintain homeostasis. Key to this is the ability for HSCs, at a population level, to self-renew and maintain
quiescence. Central to the maintenance of quiescence and to a functional stem cell pool is regulation of cell
cycle entry and exit. Many repressive chromatin-modifying complexes exist that target genes related to
proliferation and DNA replication. Perturbations in the maintenance of quiescence or differentiation can lead to
bone marrow failure or malignant transformation. We have recently demonstrated that the chromatin scaffolding
protein Sin3B is essential for the maintenance of functional HSCs in mice. Sin3B recruits histone deacetylases
and through interaction with sequence specific transcription factors modulates local chromatin at discrete
genomic loci and represses transcription. Loss of Sin3B diminishes HSCs ability to maintain quiescence and
properly differentiate in a competitive transplantation setting. This proposal seeks to understand the Sin3B-
dependent transcriptional network necessary for maintenance of HSC function. Additionally, we seek to translate
these studies to Acute Myeloid Leukemia, a malignancy characterized by rapid proliferation of blasts that are
blocked in differentiation. Specifically, it is thought that patients relapse due to the presence of chemotherapy-
resistant Leukemic Stem Cells (LSCs). These LSCs have many similarities to HSCs including quiescence and
self-renewal properties, which is hypothesized to be responsible for their resistance to conventional
chemotherapy. We propose to understand the role Sin3B plays in maintaining AML LSCs and to determine if
targeting of Sin3B presents a novel therapeutic strategy to sensitize LSCs to treatment. This proposal aims to
couple acute deletion of Sin3B with chemotherapy treatment to assess if relapse in AML can be abrogated
through selective targeting of LSCs.

## Key facts

- **NIH application ID:** 10399347
- **Project number:** 3F31CA232659-03S1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Alexander Arnuk
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $13,912
- **Award type:** 3
- **Project period:** 2018-09-11 → 2022-01-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399347

## Citation

> US National Institutes of Health, RePORTER application 10399347, Sin3B’s role in coordinating cell cycle exit and differentiation in hematopoiesis - Funded Extension (3F31CA232659-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10399347. Licensed CC0.

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