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  • Kelly, GL (author)

Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53

  • Article/chapterEnglish2014

Publisher, publication year, extent ...

  • 2014-01-06
  • Cold Spring Harbor Laboratory,2014

Numbers

  • LIBRIS-ID:oai:prod.swepub.kib.ki.se:128029455
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:128029455URI
  • https://doi.org/10.1101/gad.232009.113DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • The transcriptional regulator c-MYC is abnormally overexpressed in many human cancers. Evasion from apoptosis is critical for cancer development, particularly c-MYC-driven cancers. We explored which anti-apoptotic BCL-2 family member (expressed under endogenous regulation) is essential to sustain c-MYC-driven lymphoma growth to reveal which should be targeted for cancer therapy. Remarkably, inducible Cre-mediated deletion of even a single Mcl-1 allele substantially impaired the growth of c-MYC-driven mouse lymphomas. Mutations in p53 could diminish but not obviate the dependency of c-MYC-driven mouse lymphomas on MCL-1. Importantly, targeting of MCL-1 killed c-MYC-driven human Burkitt lymphoma cells, even those bearing mutations in p53. Given that loss of one allele of Mcl-1 is well tolerated in healthy tissues, our results suggest that therapeutic targeting of MCL-1 would be an attractive therapeutic strategy for MYC-driven cancers.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Grabow, S (author)
  • Glaser, SP (author)
  • Fitzsimmons, L (author)
  • Aubrey, BJ (author)
  • Okamoto, T (author)
  • Valente, LJ (author)
  • Robati, M (author)
  • Tai, L (author)
  • Fairlie, WD (author)
  • Lee, EF (author)
  • Lindstrom, MSKarolinska Institutet (author)
  • Wiman, KGKarolinska Institutet (author)
  • Huang, DCS (author)
  • Bouillet, P (author)
  • Rowe, M (author)
  • Rickinson, AB (author)
  • Herold, MJ (author)
  • Strasser, A (author)
  • Karolinska Institutet (creator_code:org_t)

Related titles

  • In:Genes & development: Cold Spring Harbor Laboratory28:1, s. 58-701549-54770890-9369

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