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Although IMPDH inhibitors are widely used as effective immunosuppressants, their antitumor effects have not been proven in the clinical setting. Here, we found that acute myeloid leukemias (AMLs) with MLL\u2010fusions are susceptible to IMPDH inhibitors\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    . We also showed that alternate\u2010day administration of IMPDH inhibitors suppressed the development of MLL\u2010AF9\u2010driven AML\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    without having a devastating effect on immune function. Mechanistically, IMPDH inhibition induced overactivation of Toll\u2010like receptor (TLR)\u2010TRAF6\u2010NF\u2010\u03baB signaling and upregulation of an adhesion molecule VCAM1, which contribute to the antileukemia effect of IMPDH inhibitors. Consequently, combined treatment with IMPDH inhibitors and the TLR1\/2 agonist effectively inhibited the development of MLL\u2010fusion AML. These findings provide a rational basis for clinical testing of IMPDH inhibitors against MLL\u2010fusion AMLs and potentially other aggressive tumors with active TLR signaling.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202115631","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T07:41:32Z","timestamp":1669880492000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["IMPDH inhibition activates TLR\u2010VCAM1 pathway and suppresses the development of MLL\u2010fusion 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