Genes upregulated in healthy HSCs included several involved in B cell differentiation, such as RAG1 and RAG2 mediating immunoglobulin gene segment recombination, and the B cell-specific transcription factor PAX5, whereas those upregulated in AML, and to a lesser extent in MDS and CMML HSCs were involved in myeloid differentiation, such as the cathepsins CTSA and CTSD (Fig. 1a). Here, CTSD is linked to acute myeloid leukemia.