# Single cell characterization of human acute myeloid leukemia

> **NIH NIH F32** · STANFORD UNIVERSITY · 2021 · $85,572

## Abstract

A. Project Summary
Acute myeloid leukemia (AML) is an aggressive and often fatal hematologic neoplasm. Despite cytotoxic
chemotherapy and allogeneic transplantation, patients often succumb to resistant disease, which is reflected by
a poor 5-year survival rate of between 30-40%. Numerous studies suggest that AML is organized in a cellular
hierarchy with a rare, self-renewing, leukemic stem cell (LSC) giving rise to the remaining leukemic blasts. The
AML LSC is thought to initiate and maintain leukemia in humans, and therefore needs to be eliminated in order
to achieve cure. Unfortunately, LSCs are poorly defined, which has limited the ability to directly connect LSCs
with poor clinical outcomes. It is not known if LSCs are prevalent in the majority of AML patients, and if they
express specific surface markers that can be used for disease monitoring and/or as therapeutic targets. There
is a critical need to improve our methods for isolating and studying these clinically relevant cells in AML. The
long-term goal is to improve AML outcomes by developing cell-specific monitoring strategies and patient-specific
anti-leukemia therapies. To address this goal, the next step and overall objective of this application is to
rigorously dissect the cellular heterogeneity of AML through single cell gene and protein expression analysis and
large-scale in silico cytometry. The central hypothesis is that LSCs are enriched in rare, disease maintaining,
AML sub-populations and can be purified using cell specific surface markers. This hypothesis was formulated
based on single cell analysis of primary AML patient samples. A rare sub-population of AML cells was identified
that is enriched for stem cell gene expression programs and whose gene expression signature is correlated with
shorter overall survival. The rationale for the proposed research is that identifying and purifying LSCs are
necessary for understanding leukemogenesis and treatment resistance, and in turn designing curative therapies.
Guided by strong preliminary analysis, the central hypothesis will be tested by pursuing two specific aims. The
first aim will rigorously dissect the cellular heterogeneity of AML using combined single cell transcriptomic and
proteomic analysis in order to design a surface marker panel to isolate and study AML LSCs. The second aim
will construct a comprehensive cellular landscape of human AML using large scale cellular deconvolution of bulk
gene expression data. The overall contribution is expected to be the development of an actionable LSC
immunophenotyping panel, and discovery of a newly defined, clinically relevant LSC-enriched sub-population in
human AML. This contribution will be significant because it will allow us to not only improve patient outcomes by
optimizing disease monitoring strategies but it will also facilitate the design of curative, patient-specific therapies
in AML.

## Key facts

- **NIH application ID:** 10150461
- **Project number:** 5F32CA250304-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Asiri Ediriwickrema
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $85,572
- **Award type:** 5
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150461

## Citation

> US National Institutes of Health, RePORTER application 10150461, Single cell characterization of human acute myeloid leukemia (5F32CA250304-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10150461. Licensed CC0.

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