Single-cell immune landscape of measurable residual disease in acute myeloid leukemia

Abstract

Measurable residual disease (MRD) is a powerful prognostic factor for relapse in acute myeloid leukemia (AML). We applied the single-cell RNA sequencing to bone marrow (BM) samples from MRD-positive (n = 20) and MRD-negative (n = 12) patients after allogeneic hematopoietic stem cell transplantation. A comprehensive immune landscape with 184,231 cells was created. Compared with CD8+ T cells enriched in MRD-negative patients (MRD-_CD8), those enriched in MRD-positive patients (MRD+_CD8) showed lower expression levels of cytotoxicity-related genes. Monocyte clusters (MRD+_M) and B-cell clusters (MRD+_B) were both enriched in MRD-positive patients. Conversion from an MRD-positive state to an MRD-negative state accompanied with the increase of MRD-_CD8 clusters and vice versa. MRD-enriched cell clusters employed the macrophage migration inhibitory factor pathway to regulate MRD-_CD8 clusters. These firstly revealed characteristics of immune cell landscape in MRD positivity, which will enable a better understanding of the immune mechanisms for MRD conversion.