Signals emanating from the bone marrow microenvironment are crucial for the survival, stem cell self-renewal capacity and pathogenesis of haematological malignancies. Yet, many of the local and direct interactions between stromal cells and haematopoietic cells with leukaemia cells in the microenvironment that facilitate leukaemogenesis remain to be identified. Using single-cell RNA sequencing (scRNA-seq), Sharma et al. have now discovered that bone marrow osteolineage cells are a producer of taurine in the leukaemia niche, which in turn drives leukaemia stem cell (LSC) survival and self-renewal.
The authors chose to focus further experiments on SLC6A6, which encodes TAUT, a transporter of taurine and β-alanine, since it was also upregulated in human blast crisis-phase chronic myeloid leukaemia stem cells, suggesting a more universal role. Next, using scRNA-seq analysis of CD45− stromal cells from human AML bone marrow aspirates, the authors found that the expression of enzymes required for taurine biosynthesis (CDO1 and CSAD) were restricted to mesenchymal stromal cell (MSC) and osteolineage cell populations. Furthermore, knocking down CDO1 expression in MSC cultures derived from patient AML bone marrow aspirates reduced the survival and colony-forming capacity of co-cultured AML cells from the same patient.
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