# The Role of miR-29b in NK cell Development in Acute Myeloid Leukemia

> **NIH NIH K22** · OHIO STATE UNIVERSITY · 2020 · $186,840

## Abstract

PROJECT SUMMARY/ABSTRACT
Immune evasion is a major mechanism of acute myeloid leukemia (AML) persistence, and represents a barrier
for long-term clinical success. There is a critical need for improved therapies for AML since despite recent
therapeutic advances, the 5-year-survival rate is still less than 30% overall. Natural killer (NK) cells represent
an encouraging frontier for novel anti-cancer treatments as they have the innate ability to identify, target, and
kill cancer cells without prior sensitization. Our previous studies have identified a defect in a specific
population of maturing NK cells in both a murine model of AML and in AML patients. This defect appears to be
mediated by the overexpression of microRNA (miR)-29b, a potential regulator of TBX21 and EOMES, two key
transcription factors important for NK cell development. We believe at least part of this negative regulation is
due to soluble tumor-derived signals which drive this overexpression of miR-29b in NK cells. We hypothesize
that soluble ligands from leukemic blasts both directly elevate miR-29b through the export of extracellular
vesicles, as well as indirectly through the activation of the aryl hydrocarbon receptor (AHR), a ligand activated
transcription factor expressed in immature NK cells. We have previously shown that AHR modulates early NK
cell development, and preliminary studies indicate AHR may bind to and regulate the miR-29b promoter. This
preliminary work led to the following specific aims: 1) To determine the mechanism(s) and impact of NK cell
dysregulation of miR-29b in AML. 2) To determine the impact of blocking the aryl hydrocarbon receptor
pathway on NK cell function in vivo. These aims are important for both defining how AML is able to evade
innate immunity, and identifying potential targets for therapeutic intervention. The studies outlined in this
proposal will form a solid foundation from which the PI will begin building a successful independent career in
the field of tumor immunology and advancing the knowledge and treatment options of cancer. To achieve
these goals, the PI has established an extensive network of collaborators and world-class mentors to guide her
through the early stages of her career. Additionally, the PI has outlined numerous meetings, courses and
educational enrichment activities supported by her institution to further increase the success and effectiveness
of her career. Together, the aforementioned activities with this research proposal will provide the framework for
her transition into an independent environment and long-term career goals of translating these discoveries to
novel therapeutics to improve patient outcomes.

## Key facts

- **NIH application ID:** 9973154
- **Project number:** 5K22CA218466-03
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Bethany Mundy-Bosse
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $186,840
- **Award type:** 5
- **Project period:** 2018-08-15 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973154

## Citation

> US National Institutes of Health, RePORTER application 9973154, The Role of miR-29b in NK cell Development in Acute Myeloid Leukemia (5K22CA218466-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9973154. Licensed CC0.

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