# Interrogation of the oxidative-stress-induced leukemia program in vivo using metabolic imaging

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $679,961

## Abstract

PROJECT SUMMARY/ABSTRACT
Acute myeloid leukemia (AML) is a genetically complex and heterogeneous set of diseases characterized by a
diverse set of mutations. Although many patients initially respond to treatment, many end up relapsing. Over the
last decade, an appreciation of the genetic diversity and clonal hierarchy in AML has opened the door to novel
therapeutic targets and therapeutic approaches to specific AML subtypes. Moreover, AML has been found to
bear unique metabolic features with therapeutic implications. Most importantly, mutations in the enzymes
isocitrate dehydrogenase (IDH1/2) have led to clinically approved drugs. However, many patients become
resistant to this therapy as well, further underscoring the need for new strategies to target dysregulated
metabolism in leukemia. Through the development of novel microcoil platforms to explore leukemia metabolism
with HP MR (Jeong et al. Science Advances 2017) we have identified a new metabolic vulnerability in the
glycolytic metabolism of leukemia (Jeong et al. Cell Metabolism 2021). This reliance on glycolytic metabolism
alters not only glucose flux to lactate, but also one-carbon flux through the serine pathway, which facilitates the
metabolism of glutamine. Moreover, we found that genetically targeting or pharmacologically inhibiting the
enzyme that mediates flux through this pathway (PHGDH) capitalizes on a new vulnerability in these cells.
Importantly, this targeting does not affect normal hematopoietic cell growth. Thus, building upon extensive
collaboration between our labs and ample preliminary data, we aim to employ innovative approaches to study
metabolism (Keshari Lab), including by developing non-invasive probes to measure changes in glycolysis and
oxidative stress with hyperpolarized magnetic resonance imaging. This metabolism will be characterized in well-
defined models of AML (Kharas Lab), with both genetic and pharmacological modulation, in order to develop a
strategy to assess leukemia-stem-cell-driven AML metabolism and the inhibition of serine metabolism.
Altogether, these studies will result in new mechanistic insights and novel cancer therapies.

## Key facts

- **NIH application ID:** 10876462
- **Project number:** 5R01CA283578-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Kayvan R Keshari
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $679,961
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876462

## Citation

> US National Institutes of Health, RePORTER application 10876462, Interrogation of the oxidative-stress-induced leukemia program in vivo using metabolic imaging (5R01CA283578-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10876462. Licensed CC0.

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