# Interrogating oncogene-dependency and mutation order in FLT3 mutant AML

> **NIH NIH K99** · SLOAN-KETTERING INST CAN RESEARCH · 2021 · $142,467

## Abstract

PROJECT ABSTRACT/SUMMARY
CANDIDATE: I am a postdoctoral fellow in the laboratory of Dr. Ross Levine in the Human Oncology and
Pathogenesis Program at Memorial Sloan Kettering Cancer Center. My previous PhD research offered me the
opportunity to develop the experimental and computational skills necessary to assess cellular crosstalk in the
tumor microenvironment. My current research extends these skills to the study of mutation order, and
oncogene-dependency in subpopulations of leukemic cells. To gain insights into these processes I developed
novel, multi-recombinase mouse models of oncogene-activation and dependency as well as new lineage tracing
tools that allow for functional interrogation of clonal evolution. My proposed research will provide a strong
foundation for independent research following the K99 phase of this grant. My long-term career goal is to
identify molecular mechanisms driving leukemogenesis, including interactions between AML subclones in vivo
and the role of sequential mutational acquisition. To achieve these goals I have developed a career plan that
will 1) bolster my technical skills and scientific scope, 2) improve my presentation and communication skills, 3)
cultivate professional relationships and networking, and 4) prepare me for mentoring future trainees.
RESEARCH: The receptor tyrosine kinase, FLT3, is the most commonly mutated gene in acute myeloid
leukemia. Mutations in FLT3 are often found with low variant allele frequency, suggesting these mutations
occur as late, subclonal events. Despite their presence as a minor clone, FLT3 mutations are poor prognostic
markers and the target of several recently approved clinical compounds. These inhibitors lead to some
transient clinical success, yet patients invariably relapse and develop resistant, calling into question the
necessity of FLT3 mutation in disease progression. I aim to determine the dependency of FLT3 mutations in
disease, and propose methods to assess the functional contributions of subclonal mutations to disease
progression. The specific aims are: 1) determining the genomic context for FLT3 oncogene-dependency in
AML, 2) identifying novel therapeutic vulnerabilities in FLT3-driven AML, and 3) investigating the role of
mutation order and clonal crosstalk in leukemic disease.
ENVIRONMENT: The Levine laboratory is a part of the Human Oncology and Pathogenesis Program
(HOPP) at Memorial Sloan Kettering Cancer Center, a state of the art cancer research institute. The Levine lab
is also a member of the Center for Epigenetic Research, and the primary mentor Dr. Levine, is the head of the
Center for Hematologic Malignancies. These affiliations provide a rich set of collaborative, technical and
scientific resources to execute the research and career development proposed here.

## Key facts

- **NIH application ID:** 10126822
- **Project number:** 5K99CA248460-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Robert Lyle Bowman
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $142,467
- **Award type:** 5
- **Project period:** 2020-04-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126822

## Citation

> US National Institutes of Health, RePORTER application 10126822, Interrogating oncogene-dependency and mutation order in FLT3 mutant AML (5K99CA248460-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10126822. Licensed CC0.

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