Spatial transcriptomics in paediatric and adult acute myeloid leukaemia: unravelling the bone marrow microenvironment

Acute myeloid leukaemia (AML) urgently requires novel therapeutic strategies. However, immunotherapy has so far shown limited results, and the cellular interactions driving immune evasion remain poorly characterized. To address this gap, we applied Xenium imaging-based spatial transcriptomics to 62 formalin-fixed paraffin-embedded bone marrow (BM) biopsies from AML patients (26 children, 18 adults) and non-leukemic controls (9 children, 9 adults), yielding 474,580 high-quality single-cell spatial transcriptomes. This enabled accurate characterization of the BM composition in situ, identifying a substantially higher frequency of stromal cells (median 5%, range 2-19%) and macrophages (3%, 0.3-21%) compared to typical BM aspirate-based analyses. Importantly, fusion probes allowed identification of cells carrying the RUNX1::RUNX1T1 fusion, and spatial analysis revealed a distinct organization of cellular niches in the healthy BM, which is lost in AML. The insights generated by this approach are of great value to characterize cell-cell interactions related to immune evasion and to identify potential therapeutic targets, paving the way for successful immunotherapy in AML.

Publication History

Article published online:
09 May 2025