Distinguishing relapse from sustained remission in acute myeloid leukemia. Lineage-specific developmental stage distributions

We characterize bone marrow cell populations at minimal residual disease (MRD) by their distribution across hematopoietic developmental stages within each major lineage. Using the BoneMarrowMap atlas (263.159 reference cells, 24 broad cell types) as a coordinate system, we assign each cell in a patient’s MRD sample to a developmental stage along one of five lineages (myeloid, erythroid, B-cell, T/natural killer, dendritic). Each patient is then represented by stage histograms compared to four reference populations (healthy control, diagnosis, relapsed MRD, sustained-remission MRD) via uncertainty-normalized distances and adjacent-stage concordance τNN. Applied to 47 patients from four independent cohorts (Ennis et al. 2023, Lambo et al. 2023, Naldini et al. 2023, Beneyto-Calabuig et al. 2023; accessed through the Zeng et al. 2025 compendium), 28 of whom relapsed and 19 of whom remained in sustained remission, the combined feature set achieves area under the receiver operating characteristic curve (AUC) 0.95 by leave-one-out cross-validation, 0.93 by leave-two-out, and 0.92 by repeated 70/30 stratified splits. The dominant signal is developmental maturity at MRD: relapsing patients show a higher fraction of terminally differentiated cells across all lineages—particularly plasmacytoid dendritic cells and monocytes—while sustained-remission MRD retains more primitive cells and resembles healthy marrow. These signatures are measurable from standard single-cell RNA sequencing and a public reference atlas.1