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However, relapsed and refractory disease remains a significant problem. The chemotherapy burden experienced by these patients makes the translational development of non-genotoxic experimental therapies attractive. We previously reported that the anti-helminth drug mebendazole induces degradation of the transcription factor MYB and has potent anti-AML activity. In the present study, we use CRISPR drop-out screening to identify genes encoding the proapoptotic regulators BAK and NOXA as hits conferring resistance to mebendazole activity in AML cells. Conversely, targeting MCL1 with a BH3-mimetic significantly enhanced the anti-AML activity of mebendazole in both AML cell lines in vitro and pediatric patient-derived xenograft (PDX) AML cells ex vivo. Treatment of mice transplanted with THP-1 AML cells or aggressive infant PDX AML cells with this drug combination significantly impaired disease progression in vivo. Our data indicate that mebendazole-induced MYB degradation in combination with MCL1 targeting is a novel non-genotoxic therapeutic strategy for pediatric AML.<\/jats:p>","DOI":"10.1038\/s41419-026-08847-2","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:13:10Z","timestamp":1778623990000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MCL1 inhibition to enhance the efficacy of MYB targeting in pediatric acute myeloid leukemia"],"prefix":"10.1038","volume":"17","author":[{"given":"Alexia","family":"Tsakaneli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelia","family":"Che","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemence","family":"Virely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryony","family":"McCord","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6146-2124","authenticated-orcid":false,"given":"Luca","family":"Gasparoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aerin","family":"Loe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5797-1268","authenticated-orcid":false,"given":"Kent","family":"Fung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Ciampa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuriye Meryem","family":"Alver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Bartram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"O\u2019Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Mansour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1760-6880","authenticated-orcid":false,"given":"Owen","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"8847_CR1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1080\/14737140.2021.1841640","volume":"21","author":"AE Hoffman","year":"2021","unstructured":"Hoffman AE, Schoonmade LJ, Kaspers GJ. 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