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Targeting of MCL-1 ...
Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53
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Kelly, GL (author)
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Grabow, S (author)
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Glaser, SP (author)
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Fitzsimmons, L (author)
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Aubrey, BJ (author)
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Okamoto, T (author)
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Valente, LJ (author)
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Robati, M (author)
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Tai, L (author)
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Fairlie, WD (author)
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Lee, EF (author)
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- Lindstrom, MS (author)
- Karolinska Institutet
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- Wiman, KG (author)
- Karolinska Institutet
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Huang, DCS (author)
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Bouillet, P (author)
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Rowe, M (author)
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Rickinson, AB (author)
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Herold, MJ (author)
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Strasser, A (author)
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(creator_code:org_t)
- 2014-01-06
- 2014
- English.
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In: Genes & development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 28:1, s. 58-70
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http://genesdev.cshl...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- 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.
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Kelly, GL
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Grabow, S
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Glaser, SP
-
Fitzsimmons, L
-
Aubrey, BJ
-
Okamoto, T
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show more...
-
Valente, LJ
-
Robati, M
-
Tai, L
-
Fairlie, WD
-
Lee, EF
-
Lindstrom, MS
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Wiman, KG
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Huang, DCS
-
Bouillet, P
-
Rowe, M
-
Rickinson, AB
-
Herold, MJ
-
Strasser, A
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show less...
- Articles in the publication
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Genes & developm ...
- By the university
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Karolinska Institutet