# Development of a Universal Assay for Minimal Residual Disease in Acute Myeloid Leukemia using Duplex Sequencing

> **NIH NIH R44** · TWINSTRAND BIOSCIENCES, INC. · 2021 · $859,730

## Abstract

Acute myeloid leukemia (AML) is a morbid condition, with over 20,000 new cases and 10,000 deaths annually
in the U.S. While the majority of patients achieve remission, most harbor minimal amounts of residual disease
(MRD) that will ultimately lead to relapse. The ability to detect MRD is important as its presence is associated
with increased risk of relapse and death, and there is considerable interest in modulating treatment intensity
based on the presence or absence of MRD. Unfortunately, current MRD detection methods suffer from variable
sensitivity, non-uniform performance across laboratories, and lack of broad applicability to all patients. There is
an urgent, unmet need for a better MRD detection method, which could substantially benefit patients as well as
other stakeholders. Next generation sequencing (NGS) permits detection of genetic aberrations on the
subclonal level. As virtually all AML harbors mutations, NGS could be a platform for a “universal” MRD assay.
Unlike other detection methods, NGS would reveal specific mutations and could suggest targeted therapies.
Enthusiasm for NGS for MRD detection has, until now, been tempered by the relatively poor sensitivity of this
method. Duplex Sequencing, the most accurate NGS technology, can change the paradigm for MRD detection.
Members of our team pioneered this proprietary technology and demonstrated in proof-of-principal studies that
it can accurately detect leukemic clones at extremely low levels. In Phase I of this Fast Track application, we
will refine steps in our sequencing procedures to facilitate industrial-scale deployment of our MRD assay and
validate analytical performance. In Phase II, we assess our assay's performance based on banked AML
samples. In Aim 1, we focus on whether our assay is prognostic of disease relapse. In Aim 2, we compare our
assay to flow cytometry, the current gold standard for MRD detection. In Aim 3, we compare performance of
our assay on paired bone marrow and peripheral blood samples to determine if we can achieve comparable
results less invasively. The final product will be a robust, cost-effective, and implementable Laboratory
Developed Test (LDT) ready for commercial deployment. This product will be widely useful for patients,
oncologists, and payers alike by helping direct cutting-edge therapies to the patients most likely to benefit,
while sparing others unnecessary medical and financial toxicities. It will allow researchers and pharmaceutical
companies to rapidly evaluate novel therapies, permitting future clinical trials to be smaller and less costly.
AML takes the lives of thousands of patients every year. Patients die both from the disease and from the
aggressive treatment. Having an ultra-accurate “universal” test to detect MRD would allow for improved
prognostication and would pave the way for more efficacious personalized treatment. We fundamentally
believe that such a test is necessary and well within our reach, and that our team is positio...

## Key facts

- **NIH application ID:** 10076806
- **Project number:** 5R44CA233381-04
- **Recipient organization:** TWINSTRAND BIOSCIENCES, INC.
- **Principal Investigator:** Jerald Patrick Radich
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $859,730
- **Award type:** 5
- **Project period:** 2018-07-16 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076806

## Citation

> US National Institutes of Health, RePORTER application 10076806, Development of a Universal Assay for Minimal Residual Disease in Acute Myeloid Leukemia using Duplex Sequencing (5R44CA233381-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10076806. Licensed CC0.

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