AUY922 effectively targets against activated B cell subtype of diffuse large B-cell lymphoma and low-grade lymphoma cells harboring genetic alteration-associated nuclear factor-B activation

Hui Jen Tsai, Neng Yao Shih, Sung Hsin Kuo, Ann Lii Cheng, Hui You Lin, Tsai-Yun Chen, Kung-Chao Chang, Sheng Fung Lin, Jeffrey S. Chang, Li Tzong Chen

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Recurrent genetic alterations that are frequently observed in some low-grade lymphomas, such as activated B cell subtype of diffuse large B-cell lymphoma (ABC-DLBCL) and mucosa-associated lymphoid tissue type lymphoma (MALT lymphoma) are usually associated with nuclear factor-B (NF-B) activation and confer resistance to therapy. In this study, we investigated the therapeutic efficacy and molecular mechanisms of AUY922, a novel Hsp90 inhibitor, in representative cell lines OCI-Ly3 (ABC-DLBCL) and MA-1 (a low-grade lymphoma cell line with t(14;18)/IgH-MALT1translocation) to explore its potential use in the treatment of refractory B-cell lymphoma. Our results showed that AUY922 effectively induced growth inhibition and apoptosis of OCI-Ly3 and MA-1 cells, which were accompanied by down-regulation of the expression levels of NF-B and Bcl-2 family proteins, as well as molecules of multiple signaling pathways involving cell proliferation, growth and survival. The growth inhibitory effect of AUY922 was further confirmed in a mouse xenograft model. These findings indicate the potential use of AUY922 in B cell lymphomas.

Original languageEnglish
Pages (from-to)2674-2682
Number of pages9
JournalLeukemia and Lymphoma
Volume56
Issue number9
DOIs
Publication statusPublished - 2015 Sep 2

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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