# Targeting SYK Kinase in AML

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

## Abstract

Project Summary/Abstract 
New targeted therapies are urgently needed for acute myeloid leukemia (AML), where little progress has been 
made in improving long-term patient survival despite significant inroads into understanding the molecular 
pathogenesis of this disease. We previously discovered spleen tyrosine kinase (SYK) as a new target in AML, 
with FLT3-ITD a biomarker of response to SYK inhibitors in AML cells. These findings become immediately 
translatable as numerous SYK inhibitors are entering clinical trials for patients with cancer, including AML. The 
translation of SYK inhibitors to the clinic for patients with AML is the focus of this project. In Aim 1 of this 
proposal, we will study SYK activation in AML cell lines and patient blasts to determine whether SYK activation 
promotes resistance to current AML therapy. In this Aim, we will also determine whether SYK inhibitors 
synergize with drugs currently used to treat patients with AML, both in vitro and in vivo, to inform second- 
generation SYK inhibitor clinical trials. In Aim 2, we will test specific hypotheses and conduct unbiased 
functional genomic studies to identify resistance mechanisms to SYK inhibitors in AML. We expect that these 
experiments will inform new drug combinations for testing with SYK inhibitors. Aim 3 will focus on performing 
the correlative biology studies for two Phase I/II clinical trials testing SYK inhibitors in patients with AML. In this 
Aim, we will use next-generation sequencing of panels of leukemia-associated genes, immunohistochemistry 
and intracellular phospho-specific flow cytometry to measure activated SYK, BH3 profiling, and gene 
expression signature assays to identify biomarkers of response to SYK inhibitors and to confirm target 
inhibition using AML samples from patients treated on the clinical trial. At the completion of this study, we 
expect to confirm on-target, anti-leukemia activity of a SYK inhibitor in patients with AML and to inform second- 
generation clinical trials through the identification of drug combinations with SYK inhibitors and through the 
identification of biomarkers of response in patients with AML treated with a SYK inhibitory drug.

## Key facts

- **NIH application ID:** 10220876
- **Project number:** 5P50CA206963-06
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Kimberly Stegmaier
- **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/10220876

## Citation

> US National Institutes of Health, RePORTER application 10220876, Targeting SYK Kinase in AML (5P50CA206963-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10220876. Licensed CC0.

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