348: v96: A 96-mutation plasma DNA test to track residual AML through transplant

Wang Y et al et al., PNAS - This episode covers a PNAS study describing v96, a personalized plasma cell-free DNA assay that tracks up to 96 patient-specific mutations to sensitively quantify measurable residual disease (MRD) in AML patients before and after allogeneic hematopoietic cell transplantation. Key terms: cell-free DNA, measurable residual disease, acute myeloid leukemia, hematopoietic cell transplantation, duplex sequencing.

Study Highlights:
The personalized v96 assay detected residual leukemia in 100% of 30 AML patients at clinical remission, compared with 20% by flow cytometry. Plasma cfDNA was more informative and sensitive than bone marrow DNA and driver mutation assays, with 90% of patients positive at 2 months posttransplant. Higher pretransplant mutant molecule counts correlated with relapse risk, and leukemic burden typically fell only after immunosuppression was discontinued, consistent with a graft-versus-leukemia effect.

Conclusion:
A plasma-based multiplexed assay (v96) enables highly sensitive, noninvasive MRD monitoring in AML patients undergoing transplantation and may inform timing of immunosuppression and posttransplant interventions, though larger studies are needed to confirm clinical utility.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
A plasma - based DNA test for quantification of disease burden in acute myeloid leukemia patients undergoing bone marrow transplantation

First author:
Wang Y et al

Journal:
PNAS

DOI:
10.1073/pnas.2537987123

Reference:
Wang Y et al., A plasma-based DNA test for quantification of disease burden in acute myeloid leukemia patients undergoing bone marrow transplantation. PNAS. 2026;123(16):e2537987123. doi:10.1073/pnas.2537987123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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Episode link: https://basebybase.com/episodes/v96-plasma-ctdna-aml-transplant

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-04-21.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript’s presentation of the v96 methodology, passenger vs driver mutations, plasma vs marrow MRD detection, relapse prediction, and posttransplant immunosuppression dynamics against the original article.
- transcript topics: v96 workflow and passenger mutation panel; duplex sequencing (SaferSeqS) and error suppression; plasma vs bone marrow cell-free DNA for MRD detection; driver vs passenger mutations for MRD assessment; predictive power for relapse (352-fold difference pre-transplant); graft-versus-leukemia (GvL) dynamics and immunosuppression

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 5
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- v96 assay tracks up to 96 leukemia-specific passenger mutations in plasma cfDNA and detects residual leukemia in all patients at complete remission (CR) by v96, vs 20% by flow cyto
- plasma cfDNA mutant-allele fractions (MAF) are higher than bone marrow DNA (2.9% vs 0.42%) at CR
- pre-transplant plasma mutant molecule counts are 352-fold higher in patients who relapse compared with those who do not relapse
- post-transplant residual disease declines more rapidly after immunosuppressive therapy is discontinued, indicating graft-versus-leukemia (GvL) activity
- v96 detects MRD in 100% of patients prior to transplant, whereas driver mutations detected by SaferSeqS are found in about 48% (10/21) at the same time point; at 2 months posttrans

QC result: Pass.