# Experimental and preclinical modeling of NUP98-rearranged acute leukemia

> **NIH NIH U54** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $179,500

## Abstract

PROJECT SUMMARY - Overview
Fusion oncoproteins (FO) arising from the rearrangement of Nucleoporin 98 (NUP98) to a diverse range of
partner genes are a hallmark of multiple subtypes of high risk myeloid malignancies in children and adolescents,
including acute erythroleukemia and acute megakaryoblastic leukemia. Such leukemias are associated with poor
outcome, and more effective therapies are required. The long-term goal of this Center for Experimental and
Preclinical Modeling of NUP98 Leukemia is to determine the molecular role, and potential vulnerabilities, of
NUP98-fusion oncoproteins in leukemia through the development and interrogation of human and mouse model
systems, and to develop and test novel therapeutic approaches. The Center has assembled a consortium of
investigators with complementary expertise in genomic characterization, leukemia modeling, chromatin biology,
structural biology and preclinical modeling. The Center is led by Dr Charles Mullighan of St Jude Children’s
Research Hospital together with Project Co-Leaders Drs Scott Armstrong (Dana Farber Cancer Institute),
Taosheng Chen (St Jude), Alex Kentsis (Memorial Sloan Kettering Cancer Institute), Jeffery Klco (St Jude) and
Richard Kriwacki (St Jude). These investigators will co-Lead four projects performing experimental modeling
(Project 1), investigating chromatin biology (Project 2), phase separation (Project 3) and drug development
(Project 4) that will address the following questions and unmet needs: (1) to define how NUP98 fusions drive
leukemogenesis using complementary, integrative engineered models and proteomic, transcriptomic and
epigenomic profiles; (2) to develop genetically faithful engineered mouse, human and xenograft models of
NUP98 leukemia for mechanistic interrogation and preclinical modeling; (3) to define the macromolecular
chromatin and protein complexes assembled by NUP98 FOs; (4) to define the role of phase separation in NUP98
FO leukemogenesis; (5) to define the dependencies and vulnerabilities of NUP98-rearranged leukemic cells;
and (6) to develop more effective therapeutic strategies for NUP98-rearranged leukemia. The Center is
supported by an Administrative Core A that with an External Advisory Board will oversee project progress
interaction and reporting, a Genome Editing Core B led by Dr David Chen (City of Hope) that provides expertise
and support for CRISPR/Cas9 genome editing scans and screens; and a Chemistry Core C led by Dr Zoran
Rankovic (St Jude) that supports chemical library screen and drug design and development. This highly
integrated, interactive and synergistic Center will provide fundamental insights into the mechanisms of
oncogenesis of the different classes of NUP98 FO, and new therapeutic modalities that will be validated in
preclinical models and translated into human clinical trials. All data and resources will be made freely available
by websites, data deposition, and establishment of resource and genomic data portals to the Fus...

## Key facts

- **NIH application ID:** 10230523
- **Project number:** 3U54CA243124-01S2
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Charles G Mullighan
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $179,500
- **Award type:** 3
- **Project period:** 2019-09-19 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10230523

## Citation

> US National Institutes of Health, RePORTER application 10230523, Experimental and preclinical modeling of NUP98-rearranged acute leukemia (3U54CA243124-01S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10230523. Licensed CC0.

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