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Leukemic stem cells (LSCs), a major driver of therapy resistance, rely predominantly on mitochondrial oxidative phosphorylation (OXPHOS) for survival. Targeting mitochondrial metabolism represents a promising therapeutic strategy. This study investigated the effect of\n                      <jats:italic>Eucalyptus camaldulensis<\/jats:italic>\n                      Dehnh. leaf extract, alone and in combination with thalidomide, on mitochondrial energetics in AML cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An in vitro study was conducted using the human AML Kasumi-1 cell line. Cells were divided into four groups: control, thalidomide-treated,\n                      <jats:italic>E. camaldulensis<\/jats:italic>\n                      extract-treated, and combination-treated groups. The ethanolic extract was characterized by GC\u2013MS and HPLC. Cell viability was assessed using WST-1 assay and IC\u2085\u2080 values were calculated. Gene expression of CD34, MFN1, MFN2, OPA1, and IL-6 was quantified by qRT-PCR. ATP levels were measured by ELISA. Mitochondrial length was assessed by transmission electron microscopy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>E. camaldulensis<\/jats:italic>\n                      extract significantly reduced Kasumi-1 cell viability in a concentration-dependent manner, both alone and in combination with thalidomide. The combination demonstrated an additive cytotoxic effect (CI\u2009=\u20091). The IC\u2085\u2080 values were 197.80\u00a0\u00b5g\/mL for thalidomide, 30.26\u00a0\u00b5g\/mL for the extract, and 28.26\u00a0\u00b5g\/mL for the combination. Thalidomide alone or combined significantly downregulated IL-6 expression, while thalidomide increased MFN1 expression. The extract significantly downregulated IL-6 and mitochondrial fusion genes and reduced CD34 expression. Extract treatment decreased ATP levels and shortened mitochondrial length compared with untreated cells (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Eucalyptus camaldulensis extract disrupts mitochondrial energetics and LSC-associated pathways in AML cells. Its combination with thalidomide shows additive activity and may represent a complementary strategy to overcome metabolic-driven therapy resistance in AML.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12906-026-05503-2","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T01:55:29Z","timestamp":1786586129000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Eucalyptus camaldulensis leaf extract enhances thalidomide efficacy in acute myeloid leukemia cells through modulation of mitochondrial energetics"],"prefix":"10.1186","volume":"26","author":[{"given":"Samah E.","family":"Ismail","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf A.","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany A.","family":"Elkhedel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal M.","family":"Fakhry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman A.","family":"Khalifa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soliman M.","family":"Toto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"5503_CR1","doi-asserted-by":"publisher","first-page":"e2300229","DOI":"10.1200\/GO.23.00229","volume":"9","author":"CT Jani","year":"2023","unstructured":"Jani CT, Ahmed A, Singh H, Mouchati C, Al Omari O, Bhatt PS, Sharma R, Farooq M, Liu W, Shalhoub J, et al. 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