# Pathways of Immune Evasion in Acute Myeloid Leukemia

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $349,640

## Abstract

Project Summary/Abstract
 Acute Myeloid Leukemia (AML) is the most common adult leukemia and has a very poor prognosis; most
patients diagnosed with AML will die from this disease. AML results from uncontrolled proliferation of poorly
differentiated myeloid precursor cells. Immune therapies, including checkpoint blockade, are currently being
studied in the context of AML. Our previous work has established that the percentage of T cells present in the
bone marrow of patients with AML at the time of diagnosis correlates with overall survival, providing evidence
that the adaptive immune system, and specifically T cells, are able to recognize malignant cells. Our lab and
others have shown that AML evades attack by the immune system by suppressing T cell function. Significantly,
this functional suppression can be reversed in vitro in most cases by immune checkpoint molecule blockade.
 Previous literature has demonstrated that the exhausted state of the immune system can result from an
epigenetic program imparted on T cells after chronic stimulation. We have previously shown a role for the map
kinase pathway (MAPK) in maintaining this exhausted state in T cells present in AML. Transformation of cells to
AML results from a combination of mutations affecting proliferation, differentiation and epigenetic state. For this
reason, drugs targeting signaling and epigenetic state are approved or are being actively studied for the
treatment of AML.
 For this project, our long-term goals are to provide a better understanding of functional T cell exhaustion
and its relevance in AML. Our immediate goal is to study the role of the MAPK pathway, DNA methyltransferases
and the epigenetic reader BET proteins in T cell exhaustion in the context of AML. We will conduct these studies
with the central hypothesis that immune evasion via T cell exhaustion in AML is imparted by signaling pathways
such as MEK and epigenetic states in T cells and that targeting these pathways in AML will reverse immune
suppression. To accomplish this goal, we propose the following three aims: 1) Understand the role of the MAPK
pathway on T cell function in AML. This will consist of mechanistic studies in T cells, but also study tumor and
other lymphoid and myeloid populations in the immune microenvironment of AML. 2) Assess the impact of
epigenetic pathways on the immunological function of T cells in mouse models of AML. Based on our preliminary
data we will focus on DNA methylation and BET protein function. 3) Define cells and pathways of immune
suppression in the tumor microenvironment of human AML. We will study a cell type associated with T cell
suppression in patient samples. We will also study effects of MEK, BET and DNMT inhibitors on patient samples.
 Together these experiments will give us a better understanding of the biology of T cell exhaustion in AML
disease. Importantly, results from these studies will have impact on treatment of this lethal disease by allowing
rational design of ...

## Key facts

- **NIH application ID:** 10444630
- **Project number:** 1R01CA262145-01A1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Evan Ferguson Lind
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $349,640
- **Award type:** 1
- **Project period:** 2022-03-18 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444630

## Citation

> US National Institutes of Health, RePORTER application 10444630, Pathways of Immune Evasion in Acute Myeloid Leukemia (1R01CA262145-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10444630. Licensed CC0.

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