# Preclinical Validation of Personalized Molecular Assays for Measurable Residual Disease Monitoring in Pediatric AML

> **NIH NIH K08** · UNIVERSITY OF COLORADO DENVER · 2023 · $227,905

## Abstract

PROJECT SUMMARY/ABSTRACT
My long-term career goal is to improve outcomes for pediatric patients with acute myeloid leukemia (AML), in
part through development of improved modalities to detect residual disease and thus allow early identification
and intervention for those patients at highest risk of relapse. My clinical experience as a pediatric oncologist
specializing in treatment of myeloid malignancies informs my translational research focus in this area. This
mentored career development award will facilitate my development into an independent translational physician-
scientist by providing salary support and protected time to enhance my technical skills, knowledge base, and
personal development in digital PCR (dPCR) assay development and validation, duplex NGS technology, NGS
data analysis and bioinformatics, clinical trial design and development, networking, and collaboration. My
mentoring team comprised of Dr. Craig Jordan (primary mentor), Dr. Dan Pollyea, Dr. Mike Verneris, and Dr.
Chris Hourigan are all leaders in their respective fields and have a proven track record of fostering trainees and
junior faculty to successful academic careers. The resource-rich environment on the Anschutz Medical
Campus of the University of Colorado and the access to patient samples afforded me by the COG Myeloid
Committee further contribute to a high probability of success for the proposed patient-oriented research. AML
accounts for a disproportionate percentage of leukemia-associated morbidity and mortality in children, with
relapse the leading cause of death in these patients. Measurable residual disease (MRD) has been shown in
AML and other hematologic malignancies to be the single most valuable post-treatment predictor of relapse,
but the existing clinical assays for MRD have significant limitations such that a high proportion of children who
ultimately succumb to relapsed AML are actually MRD negative post-treatment. We hypothesize that
application of molecular MRD assays to pediatric AML disease monitoring will be a sensitive predictor of
disease burden and relapse. During the next 5 years I propose (1) to retrospectively evaluate the correlation
between relapse and MRD positivity by mutation-based and chimerism-based dPCR assays in pediatric AML
patients generally or post-transplant, respectively; (2) to retrospectively evaluate the correlation between
relapse and MRD positivity by custom duplex NGS panels in pediatric AML patients; and (3) to prospectively
validate the relapse predictive value of duplex NGS as a novel MRD modality in pediatric AML. Successful
completion of this project will pave the way toward development of molecular tools such as dPCR and duplex
NGS as improved MRD modalities that will enhance clinicians' ability to identify patients at highest risk of
relapse and intervene to prevent its occurrence. This will lead to improved survival in pediatric patients
suffering from myeloid leukemia.

## Key facts

- **NIH application ID:** 10643568
- **Project number:** 1K08CA279762-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Amanda C Winters
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $227,905
- **Award type:** 1
- **Project period:** 2023-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10643568

## Citation

> US National Institutes of Health, RePORTER application 10643568, Preclinical Validation of Personalized Molecular Assays for Measurable Residual Disease Monitoring in Pediatric AML (1K08CA279762-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10643568. Licensed CC0.

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