# Project 1: Increasing therapeutic efficacy in isocitrate dehydrongenase (IDH)–mutant acute myeloid leukemia (AML)

> **NIH NIH P50** · SLOAN-KETTERING INST CAN RESEARCH · 2022 · $367,707

## Abstract

ABSTRACT
We and others have genetically and functionally characterized the contribution of recurrent somatic alterations
to acute myeloid leukemia (AML) pathogenesis, including IDH1/IDH2 mutations. This has led to novel insights
into AML pathogenesis and led to the identification and validation of IDH1/2 inhibitors as a therapeutic
approach in AML; the first small molecule IDH1 (ivosidenib) and IDH2 (enasidenib) inhibitors are now approved
for relapsed/refractory IDH1/2 mutant AML. However, not all patients respond to IDH1/2 inhibition and a subset
of patients relapse following responses to IDH inhibition. We will use preclinical studies and analysis of primary
samples from patients treated with IDH1/2 inhibitors to delineate molecular predictors of sensitivity and
resistance to IDH inhibitors, and to test new combination therapeutic approaches to increase therapeutic
efficacy in IDH1/2-mutant AML. This will include mechanism-based clinical trials in genetically defined subsets,
including a novel, mechanism-based clinical trial combining FLT3 and IDH1/2 inhibition in patients with
concurrent mutations. Project 1 will interact with all 3 other Leukemia SPORE research projects and will utilize
all core facilities in this program. Our collaborative efforts will include genomic interrogation of patient samples,
preclinical therapeutic and mechanistic studies, and clinical trials with extensive correlative science aimed to
nominate the best combination therapeutic approaches for AML patients with IDH1/2 mutations.

## Key facts

- **NIH application ID:** 10474275
- **Project number:** 5P50CA254838-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Ross L Levine
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $367,707
- **Award type:** 5
- **Project period:** 2021-08-24 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474275

## Citation

> US National Institutes of Health, RePORTER application 10474275, Project 1: Increasing therapeutic efficacy in isocitrate dehydrongenase (IDH)–mutant acute myeloid leukemia (AML) (5P50CA254838-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10474275. Licensed CC0.

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