# Co-targeting BET Bromodomain Proteins and Aberrant Signaling in AML.

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $247,985

## Abstract

PROJECT SUMMARY
Acute myeloid leukemia (AML) comprises 20% of childhood leukemia cases. In contrast to acute lymphoblastic
leukemia (ALL), cure rates for AML remain poor with the majority of patients dying from refractory leukemia or
treatment related toxicities. In contrast to AML in older adults, genome-wide studies of AML in children,
adolescents, and young adults (AYA) revealed a lower mutational burden and highly prevalent transcription
factor fusions and RAS pathway mutations. Additionally, while transcription factor fusions are hypothesized to
promote a transcriptional signature that is permissive for AML development, experimental data suggest that
signaling mutations play a central role in driving leukemic growth in vivo. Thus, simultaneously targeting the
abnormal transcriptional program and aberrant signaling pathways in AML is a rational therapeutic approach
that is particularly relevant in children and AYA patients.
The overall goals of this proposal are to investigate the efficacy of promising drug combinations that
simultaneously target key pathways in pediatric AML and to elucidate molecular mechanisms underlying drug
synergy and resistance to these targeted approaches through the following specific aims: (1) to identify and
validate mechanisms of drug synergy and resistance to BET + MEK inhibition; and, (2) to investigate the in
vivo efficacy of this combination in patient derived xenograft (PDX) models of pediatric AML.

## Key facts

- **NIH application ID:** 10302179
- **Project number:** 1K08CA256489-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Benjamin Huang
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $247,985
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302179

## Citation

> US National Institutes of Health, RePORTER application 10302179, Co-targeting BET Bromodomain Proteins and Aberrant Signaling in AML. (1K08CA256489-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10302179. Licensed CC0.

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