# Targeting MLL/Menin in AML

> **NIH NIH P50** · DANA-FARBER CANCER INST · 2021 · $20,549

## Abstract

Abstract: 
Inappropriate expression of genes such as the homeotic (HOX) genes is found in up to 40% of cases of Acute 
Myelogenous Leukemia (AML). Two well-known genetic subsets, those with MLL-rearrangements and those 
with NPM1 mutations, are known to possess high-level expression of HOX genes and have been shown to be 
dependent on continued expression of these genes. Recent studies have defined the protein complexes that 
maintain this aberrant gene expression. Furthermore, multiple groups and pharma/biotech companies have now 
developed small molecule inhibitors of these complexes. Some of these small molecules, particularly those 
targeting DOT1L, EZH2 and Bromodomains) have recently entered early phase trials and have shown interesting 
biological and some complete clinical responses. Another approach to target chromatin associated complexes 
is inhibition of the MLL1-Menin interaction, an approach that has also been shown to reverse HOX gene 
expression. In this proposal we will characterize newly developed MLL1-Menin inhibitors and work to bring one 
of these small molecules to clinical assessment. In Specific Aim 1 we will characterize the effects on gene 
expression and chromatin state after inhibition of the MLL1-Menin interaction in MLL-rearranged and NPM1 
mutant AML cells. In Specific Aim 2 we will assess the combination of MLL1-Menin inhibitors with either 
azacitidine, DOT1L inhibitors or FLT3 inhibitors. In Specific Aim 3 we will initiate a phase 1 trial of MLL-1 Menin 
inhibitors alone and in combination with a azacitidine. These trials that will set the foundation for further 
assessment of combinations based on results from preclinical studies described here. The proposed 
experiments will propel MLL1-Menin inhibitors to clinical assessment and importantly define combination 
approaches that should be assessed in future clinical studies.

## Key facts

- **NIH application ID:** 10220875
- **Project number:** 5P50CA206963-06
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** SCOTT A ARMSTRONG
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $20,549
- **Award type:** 5
- **Project period:** 2017-09-19 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220875

## Citation

> US National Institutes of Health, RePORTER application 10220875, Targeting MLL/Menin in AML (5P50CA206963-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10220875. Licensed CC0.

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