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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