# Pathogenetic roles of USO1 in leukemogenesis

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $78,000

## Abstract

PROJECT SUMMARY
B-acute lymphoblastic leukemia (B-ALL) is the most common malignancy in children. The protein USO1 is
specifically overexpressed in B-acute lymphoblastic leukemia (B-ALL) with translocation t(4;11) MLL-AF4, which
portends a dismal prognosis. This subtype of B-ALL, derived from a primitive hematopoietic progenitor cell, is
particularly difficult to treat, even with the recently described, and generally successful, antibody- and cell-based
therapies that target the CD19 antigen. USO1 is known to be upregulated in other cancer types, and regulates
cell survival/proliferation in multiple cancer types. Studies of the cell biological role of USO1 have shown it be a
of importance in vesicular trafficking, and recent high-throughput studies have shown that USO1 is an RNA
binding protein in some cellular systems- suggesting that this protein may exhibit a novel function connecting
post-transcriptional gene regulation to vesicular processing. In this proof-of-concept grant, we hypothesize that
(1) USO1 plays a pathogenetic role in MLL-translocated leukemogenesis and that (2) USO1 is an RNA binding
protein. In this grant, we will explore the roles of USO1 in cancer using loss-of-function genetic models in a
novel in vivo system to study MLL-AF4-driven leukemia. Additionally, we will perform biochemical cross-linking
and RNA immunoprecipitation assays to determine if USO1 binds to RNA in B-ALL cell lines. The three aims
proposed are independent, self-contained, but also have significant synergy. Together, the successful
completion of the aims will uncover whether USO1 plays a pathogenetic role in leukemia, and whether its function
involves RNA-based mechanisms. These studies are uniquely suited to the R03 mechanism, which supports
small research projects that can be carried out in a short time period with limited resources. However, these
studies will also lay the groundwork for novel diagnostic, prognostic and therapeutic strategies in B-ALL.

## Key facts

- **NIH application ID:** 10359128
- **Project number:** 5R03CA251845-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Dinesh S. Rao
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $78,000
- **Award type:** 5
- **Project period:** 2021-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359128

## Citation

> US National Institutes of Health, RePORTER application 10359128, Pathogenetic roles of USO1 in leukemogenesis (5R03CA251845-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10359128. Licensed CC0.

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