{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T17:00:39Z","timestamp":1784394039650,"version":"3.55.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with poor prognosis. The <jats:italic>MYB<\/jats:italic> oncogene encodes a master transcription factor that is activated in the majority of human T-ALLs. In the present study, we have performed a large-scale screening with small-molecule drugs to find clinically useful inhibitors of <jats:italic>MYB<\/jats:italic> gene expression in T-ALL. We identified several pharmacological agents that potentially could be used to treat MYB-driven malignancies. In particular, treatment with the synthetic oleanane triterpenoids (OTs) bardoxolone methyl and omaveloxolone decreased <jats:italic>MYB<\/jats:italic> gene activity and expression of MYB downstream target genes in T-ALL cells with constitutive <jats:italic>MYB<\/jats:italic> gene activation. Notably, treatment with bardoxolone methyl and omaveloxolone led to a dose-dependent reduction in cell viability and induction of apoptosis at low nanomolar concentrations. In contrast, normal bone marrow-derived cells were unaffected at these concentrations. Bardoxolone methyl and omaveloxolone treatment downregulated the expression of DNA repair genes and sensitized T-ALL cells to doxorubicin, a drug that is part of the standard therapy of T-ALL. OT treatment may thus potentiate DNA-damaging chemotherapy through attenuation of DNA repair. Taken together, our results indicate that synthetic OTs may be useful in the treatment of T-ALL and potentially also in other MYB-driven malignancies.<\/jats:p>","DOI":"10.3389\/fonc.2023.1126354","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T04:43:08Z","timestamp":1680496988000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthetic oleanane triterpenoids suppress MYB oncogene activity and sensitize T-cell acute lymphoblastic leukemia cells to chemotherapy"],"prefix":"10.3389","volume":"13","author":[{"given":"Paloma","family":"Tejera Nevado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tajana","family":"Te\u0161an 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