# Integration of epigenetic and non-coding RNA mechanisms in leukemia

> **NIH NIH R37** · THOMAS JEFFERSON UNIVERSITY · 2021 · $356,850

## Abstract

ABSTRACT
Acute myeloid leukemia (AML) is the most common (30-40%) of all leukemias and has the poorest survival (25%)
of any leukemia. Mutations in the DNA methyltransferase DNMT3A and internal tandem duplications of the FLT3
receptor tyrosine kinase (FLT3-ITD) and are two of the most frequent events in over 50% of AML and commonly
co-occur in patients conferring increased resistance to chemotherapy, the standard treatment for this subtype of
AML. DNMT3A/FLT3-mutant AML have more adverse clinical outcome than AML with either mutation alone.
Thus, there is a dire need for a better understanding of the biological mechanisms underlying this disease to
address pressing therapeutic challenges. Our preliminary data suggest that DNMT3A/FLT3-ITD AML
downregulate innate immune signaling through Toll-like receptors (TLRs) to maintain stemness and block
differentiation. Our data also indicate that microRNA may play an important role in the dysregulation of TLR
pathways in AML cells, suggesting a novel crosstalk between epigenetic/signaling mutations, microRNA, and
innate immune signaling in AML. Despite evidence that suggests TLR signaling is an important contributor to the
pathogenesis of myelodysplastic syndrome (MDS), very little is known about TLR signaling in AML. Thus, we
are focusing on defining the mechanisms that deregulate TLR signaling in AML, understanding the
consequences of suppressed TLR signaling in AML pathogenesis, and finally whether TLR signaling can be
leveraged to treat AML.

## Key facts

- **NIH application ID:** 10198862
- **Project number:** 5R37CA226433-04
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** Sara E Meyer
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $356,850
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198862

## Citation

> US National Institutes of Health, RePORTER application 10198862, Integration of epigenetic and non-coding RNA mechanisms in leukemia (5R37CA226433-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10198862. Licensed CC0.

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