# THE ROLE OF SELENOPROTEIN SYNTHESIS PATHWAY IN ACUTE MYELOID LEUKEMIA

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $441,560

## Abstract

AML is the most common acute leukemia in adults, and it appears increasingly with age. Despite overall
improvement in the treatment of leukemia, AML still carries a devastating prognosis for elderly patients (less
than 10% of patients survive for 5 years). Thus, new therapies for AML are necessary. Using a bioinformatics
approach and a whole-genome CRISPR screening approach, we identified regulators of selenium metabolism
to be important for AML survival. Selenium is required for cells to synthesize selenocysteine, which is then used
to produce selenoproteins. Since many selenoproteins are involved in redox regulation, we hypothesized that
selenium metabolism is required for redox maintenance of AML. This hypothesis will be tested in the following
three aims. In aim 1, we will use mouse models that we have generated that have mutations in the genes we
identified in the CRISPR screen to examine the requirement of selenium metabolism in murine AML. In aim 2,
we will use a mouse model that lacks the redox regulator, which we hypothesize to be downstream of the
selenium metabolism pathway, to examine how this redox regulator promotes murine AML. In aim 3, we will
study the mechanisms we discovered in human AML patient-derived xenograft models to examine the
therapeutic potential of inhibiting selenium metabolism in AML. These genetic analyses with both murine and
human AML models should bring novel insights into how AML regulates selenium metabolism and the
therapeutic potential of targeting this mechanism.

## Key facts

- **NIH application ID:** 10880271
- **Project number:** 5R01CA255813-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Daisuke Nakada
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $441,560
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880271

## Citation

> US National Institutes of Health, RePORTER application 10880271, THE ROLE OF SELENOPROTEIN SYNTHESIS PATHWAY IN ACUTE MYELOID LEUKEMIA (5R01CA255813-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10880271. Licensed CC0.

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