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While elevated LARP1 expression has been linked to poor prognosis in acute myeloid leukemia (AML), its mechanistic role remains unclear. Using CRISPR\/Cas9-mediated\n                    <jats:italic>LARP1<\/jats:italic>\n                    knockout and multi-omics analyses, we investigated LARP1\u2019s role in AML.\n                    <jats:italic>LARP1<\/jats:italic>\n                    loss impaired proliferation, clonogenicity, and tumor growth in xenografts, and enhanced sensitivity of AML cells to 5-azacytidine and cytarabine. Polysome profiling and RNA sequencing revealed that LARP1 modulates a distinct set of transcripts involved in mitochondrial function, amino acid metabolism, and cell cycle regulation, independently of mTOR and CDK9. Proteomics analysis uncovered additional effects of LARP1 loss on immune signaling, lysosomal pathways, and protein stability, including changes not evident at the RNA level. Metabolomic profiling showed reprogramming of arginine\/creatine metabolism and depletion of pyrimidine biosynthesis intermediates. Cytidine deaminase, a known resistance factor, was downregulated across omics layers upon\n                    <jats:italic>LARP1<\/jats:italic>\n                    loss. These findings define LARP1 as a key integrator of translational regulation and metabolic control in AML, supporting leukemic cell survival and promoting drug resistance. Targeting LARP1 may uncover vulnerabilities in leukemia cells, not addressed by current therapies.\n                  <\/jats:p>","DOI":"10.1038\/s41389-026-00623-3","type":"journal-article","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T10:44:25Z","timestamp":1778928265000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-omics analysis reveals LARP1 as a key integrator of translation and metabolism in AML"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5349-1139","authenticated-orcid":false,"given":"Dominik A.","family":"Nahotko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1481-0535","authenticated-orcid":false,"given":"Emely","family":"Lopez Fajardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta H.","family":"Baran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szymon K.","family":"Filip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8491-8086","authenticated-orcid":false,"given":"Peter A.","family":"Faull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth T.","family":"Bartom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masha","family":"Kocherginsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9991-6064","authenticated-orcid":false,"given":"Peng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9608-2810","authenticated-orcid":false,"given":"Jason","family":"Miska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Saleiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elspeth M.","family":"Beauchamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9740-7573","authenticated-orcid":false,"given":"Leonidas C.","family":"Platanias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"key":"623_CR1","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1056\/NEJMra1406184","volume":"373","author":"H Dohner","year":"2015","unstructured":"Dohner H, Weisdorf DJ, Bloomfield CD. 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