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T. Milan et al.
1D), along with transient changes in ETS, MAF, and JUN families (Online Supplementary Figure S2). We also observed an increase in the expression of S100A9 and S100A8 (Figure 1E), which have been described as direct targets of CEBPb.35 It has been recently demonstrated that the ratio of these calcium-binding proteins is critical for blocking AML differentiation,18 with S100A8 opposing the differentiation promoted by S100A9, which acts through TLR4. Interestingly, and in agreement with these
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findings, while the expression of both S100A8 and S100A9 increased when KM3 was added to CD34+ cells, there was a larger increase in S100A8, changing the ratio of S100A8:S100A9 from 1.1:1 to 3.2:1, favoring inhibition of differentiation. Other CEBP members, including CEBPb, have also previously been implicated in the process of normal myeloid differentiation,36 which sug- gests that transcription factors normally present are co- opted to activate genes that are part of a leukemic tran-
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Figure 1. Continued on following page.
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haematologica | 2022; 107(1)