{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:05:10Z","timestamp":1793361910179,"version":"4.5.0"},"reference-count":97,"publisher":"American Association for Cancer Research (AACR)","issue":"7","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Leukemic blasts are immune cells gone awry. We hypothesized that dysregulation of inflammatory pathways contributes to the maintenance of their leukemic state and can be exploited as cell-intrinsic, self-directed immunotherapy. To this end, we applied genome-wide screens to discover genetic vulnerabilities in acute myeloid leukemia (AML) cells implicated in inflammatory pathways. We identified the immune modulator IRF2BP2 as a selective AML dependency. We validated AML cell dependency on IRF2BP2 with genetic and protein degradation approaches in vitro and genetically in vivo. Chromatin and global gene-expression studies demonstrated that IRF2BP2 represses IL1\u03b2\/TNF\u03b1 signaling via NF\u03baB, and IRF2BP2 perturbation results in an acute inflammatory state leading to AML cell death. These findings elucidate a hitherto unexplored AML dependency, reveal cell-intrinsic inflammatory signaling as a mechanism priming leukemic blasts for regulated cell death, and establish IRF2BP2-mediated transcriptional repression as a mechanism for blast survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>This study exploits inflammatory programs inherent to AML blasts to identify genetic vulnerabilities in this disease. In doing so, we determined that AML cells are dependent on the transcriptional repressive activity of IRF2BP2 for their survival, revealing cell-intrinsic inflammation as a mechanism priming leukemic blasts for regulated cell death.<\/jats:p>\n                    <jats:p>See related commentary by Puissant and Medyouf, p. 1617.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 1599<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-21-0956","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T14:37:01Z","timestamp":1649687821000},"page":"1760-1781","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Unleashing Cell-Intrinsic Inflammation as a Strategy to Kill AML Blasts"],"prefix":"10.1158","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4201-4227","authenticated-orcid":false,"given":"Jana 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