The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6–dependent B cell lymphomas
Open accessAbstract
We report that heat shock protein 90 (Hsp90) inhibitors selectively kill diffuse large B cell lymphomas (DLBCLs) that depend on the BCL-6 transcriptional repressor. We found that endogenous Hsp90 interacts with BCL-6 in DLBCL cells and can stabilize BCL-6 mRNA and protein. Hsp90 formed a complex with BCL-6 at its target promoters, and Hsp90 inhibitors derepressed BCL-6 target genes. A stable mutant of BCL-6 rescued DLBCL cells from Hsp90 inhibitor–induced apoptosis. BCL-6 and Hsp90 were almost invariantly coexpressed in the nuclei of primary DLBCL cells, suggesting that their interaction is relevant in this disease. We examined the pharmacokinetics, toxicity and efficacy of PU-H71, a recently developed purine-derived Hsp90 inhibitor. PU-H71 preferentially accumulated in lymphomas compared to normal tissues and selectively suppressed BCL-6–dependent DLBCLs in vivo, inducing reactivation of key BCL-6 target genes and apoptosis. PU-H71 also induced cell death in primary human DLBCL specimens.
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Cites
Ranuncolo, S. M., Polo, J. M., Dierov, J., Singer, M., Kuo, T., Greally, J., Green, R., Carroll, M., & Melnick, A. (2007) · Nature Immunology · doi:10.1038/ni1478 · Cited by 278
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Cited by
Genetics of diffuse large B-cell lymphoma
Pasqualucci, L., & Dalla-Favera, R. (2018) · Blood · doi:10.1182/blood-2017-11-764332 · Cited by 282
Breaking bad in the germinal center: how deregulation of BCL6 contributes to lymphomagenesis
Hatzi, K., & Melnick, A. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.03.001 · Cited by 183
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Metadata
- Authors
- Cerchietti, L. C., Lopes, E. C., Yang, S. N., Hatzi, K., Bunting, K. L., Tsikitas, L. A., Mallik, A., Robles, A. I., Walling, J., Varticovski, L., Shaknovich, R., Bhalla, K. N., Chiosis, G., & Melnick, A.
- Venue
- Nature Medicine
- Published
- 2009-11-22
- Volume
- 15
- Issue
- 12
- Pages
- 1369-1376
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2054861724
- Cited by
- 161
- References
- 1
- FWCI
- 5.28
- Type
- journal article
- Language
- en
- Open access
- green
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