# CUX1 pioneer factor activity is required to prevent myeloid leukemogenesis

> **NIH NIH F32** · UNIVERSITY OF CHICAGO · 2020 · $65,310

## Abstract

PROJECT SUMMARY/ABSTRACT
Myeloid malignancies comprise a heterogenous group of life-threatening clonal bone marrow
neoplasms that affect over 150,000 people in the United States alone. Current treatment
options for acute myeloid leukemia and myelodysplastic syndrome are limited, and have only
modest benefits for high-risk patients. Deletion of part or all of chromosome 7 [-7/del(7q)] is a
common cytogenetic change associated with adverse-risk prognosis and resistance to
conventional therapies. The underlying genetic mechanism(s) in [-7/del(7q)] that leads to high-
risk myeloid disease has remained a critical but unsolved question in the field. However, our lab
has identified a tumor suppressor gene, CUX1, encoded on 7q that is recurrently mutated in
myeloid disorders. CUX1 loss-of-function mutations are associated with a poor clinical
prognosis independent of chromosome 7 cytogenetic abnormalities. Despite these findings, the
endogenous role of CUX1 during hematopoiesis, and the mechanism by which it suppresses
leukemia transformation, remain unclear, presenting a major barrier to understanding how
CUX1 haploinsufficiency leads to high-risk disorders. My preliminary data suggest that CUX1 is
required in human hematopoietic stem and progenitor cells (HSPCs) to suppress proliferation
and promote erythroid development. Furthermore, my data indicate that CUX1 cooperates with
the SWI/SNF nucleosome remodeling complex in HSPCs to regulate chromosome accessibility
and promote erythroid gene expression. This proposal will utilize innovative functional genomic
approaches, coupled with developmental assays with primary human HSPCs, to define the
molecular and cellular mechanisms by which CUX1 regulates HSPC biology and differentiation.
Fulfilling this gap in knowledge will be critical to aiding the development of new therapeutic
strategies for high-risk myeloid malignancies. This proposal will also provide me with the
expertise necessary to achieve my long-term goal of becoming an independent scientist in the
field of cancer genomics. To oversee my project and career development, I have enlisted a
team of highly qualified mentors with a breadth of experience in myeloid neoplasia,
hematopoiesis, genomics, bioinformatics, and biostatistics. Together we have developed a
robust training plan that incorporates individual and group meetings, didactic coursework,
institutional resources and seminars, and attendance at international conferences to prepare me
for a career in academic science.

## Key facts

- **NIH application ID:** 9991101
- **Project number:** 1F32HL152524-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Jeffrey Lee Kurkewich
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 1
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991101

## Citation

> US National Institutes of Health, RePORTER application 9991101, CUX1 pioneer factor activity is required to prevent myeloid leukemogenesis (1F32HL152524-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9991101. Licensed CC0.

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