Dynamics of leukemic blast and immune cell populations in Acute Myeloid Leukemia

作者：Sadiksha Adhikari, Philipp Sergeev, Nemo Ikonen, Minna Suvela, Heikki Kuusanmäki, Mika Kontro, Markus Vähä‐Koskela, Caroline A. Heckman · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-3490 · 研究领域：Single-cell and spatial transcriptomics、Acute Myeloid Leukemia Research、Immune cells in cancer

Abstract Although patients with acute myeloid leukemia (AML) initially respond to standard chemotherapy, the relapse rate is high, and many subsequently develop refractory disease. This is largely due to the clonal heterogeneity and molecular diversity of the disease, such that drug resistant subclones easily develop. Thus, response to targeted therapies can be transient while the efficacy of immunotherapy remains limited. To expand treatment options, a comprehensive understanding of the clonal landscape and immune microenvironment of AML, as well as the interactions between immune and leukemic cells is essential. Previous studies utilizing single-cell RNA sequencing (scRNA-seq) have provided valuable insights, but they predominantly focused on limited, well-controlled or newly diagnosed patient cohorts. Here, we instead characterized the cellular composition, immune marker landscape, and dynamics of leukemic cells, as well as their interactions with immune cell populations at single cell resolution in a cohort of AML bone marrow (BM, n=71) and peripheral blood (n=1) samples from patients with mixed treatment histories, sampled at diagnosis (Dg, n=22), remission (Rm, n=2), and relapse/refractory (RR, n=48) stages. Among these were 26 Dg-RR, 6 Dg-Rm-RR, and 4 RR-RR longitudinal sample sets. All samples were obtained through the Finnish Hematology Research Biobank, following protocols approved by an ethical committee of the Helsinki University Hospital and in accordance with th...