Biomarkers Consortium – Measurable residual disease in acute myeloid leukemia (MRD in AML)

Validating new methods of MRD detection and quantification as a measure of response and trial endpoints in AML

The Problem
Detection of measurable residual disease (MRD) is a strong predictor of relapse in acute and chronic leukemia, but its integration into clinical trial designs and outcome measures for acute myeloid leukemia (AML) has not been standardized.
The Solution
The MRD in AML project will investigate the use of genetic tests to improve the accuracy of MRD detection approaches, help establish MRD as a validated biomarker in AML, and generate important molecular information about this disease.


Acute myeloid leukemia (AML) is a heterogeneous genetic disease. According to the National Cancer Institute (NCI), an estimated 20,240 new AML cases were diagnosed in the United States in 2021, and the five-year survival rate is less than 30% across all age groups1. The biomarkers of measurable residual disease (MRD) cover a variety of mutations, which may occur at different frequencies at diagnosis and during therapy. This project will pioneer sensitive, reproducible, and robust platforms for the measurement of MRD, which can be used to establish it as a validated surrogate endpoint for use in clinical trials. As MRD is increasingly incorporated into clinical trials and real-time patient management, validated biomarkers will support improved patient care and enhance development of novel therapies.

MRD Detection as a Strong Predictor of Relapse

Relapse from stable disease while on treatment is the primary obstacle to curing acute and chronic leukemia in the clinical setting. The detection of MRD following treatment is a direct measure of disease burden and the strongest predictor of relapse. MRD currently guides treatment decisions and is an established clinical trial endpoint in chronic myeloid leukemia (CML), and recent collaborative efforts have demonstrated its importance in acute lymphoblastic leukemia (ALL). In acute myeloid leukemia (AML) patients, the detection of MRD is also strongly associated with relapse, but it is technically more difficult to perform and standardize in AML than in CML or ALL and has not yet been integrated into clinical trial design and outcome. This project addresses that unmet need and will develop, validate, and integrate molecular diagnostics into existing AML trials and therapy.


  • Create a library of reagents against which new technologies can be tested
  • Compare new technologies for MRD measurement to paired diagnostic/remission samples upon which MRD testing has already been performed by a benchmarked method (e.g., flow cytometry)
  • Work with the AML Precision Medicine Initiative (MyeloMatch) to bring established technologies to prospective trials
  • Partner with the FDA, MyeloMatch, and pharmaceutical companies to establish testing standards and design clinical trials that can further test these technologies, to establish MRD as a surrogate endpoint for drug development
  • Through validating MRD as a biomarker in AML, better inform treatment decisions and ultimately improve patient outcomes


FNIH Announcement (February 8, 2022): FNIH Biomarkers Consortium Project Will Establish New Methods for Detecting Disease in Acute Myeloid Leukemia

1Data from NCI SEER data sheets.