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Targeting MYC and BCL2 by a natural compound for "double-hit" lymphoma.
Liu, Xiaoqian; Xu, Senlin; Zhang, Jiawei; Fan, Mingjie; Xie, Jun; Zhang, Bingfeng; Li, Hongzhi; Yu, Guohua; Liu, Yinghui; Zhang, Yuanfeng; Song, Joo; Horne, David; Chan, Wing C; Chu, Xiaoxia; Huang, Wendong.
Afiliação
  • Liu X; Department of Hematology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
  • Xu S; Molecular and Cellular Biology of Cancer Program & Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, California, USA.
  • Zhang J; Molecular and Cellular Biology of Cancer Program & Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, California, USA.
  • Fan M; Molecular and Cellular Biology of Cancer Program & Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, California, USA.
  • Xie J; Molecular and Cellular Biology of Cancer Program & Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, Duarte, California, USA.
  • Zhang B; Department of Molecular Medicine, City of Hope National Medical Center, Duarte, California, USA.
  • Li H; Department of Molecular Medicine, City of Hope National Medical Center, Duarte, California, USA.
  • Yu G; Department of Molecular Medicine, City of Hope National Medical Center, Duarte, California, USA.
  • Liu Y; Department of Pathology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
  • Zhang Y; Department of Hematology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
  • Song J; Department of Hematology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
  • Horne D; Department of Pathology, City of Hope National Medical Center, Duarte, California, USA.
  • Chan WC; Department of Molecular Medicine, City of Hope National Medical Center, Duarte, California, USA.
  • Chu X; Department of Pathology, City of Hope National Medical Center, Duarte, California, USA.
  • Huang W; Department of Hematology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
Hematol Oncol ; 40(3): 356-369, 2022 Aug.
Article em En | MEDLINE | ID: mdl-35482553
ABSTRACT
Concurrent translocations of MYC and BCL2 lead to abnormal expression of both oncoproteins, which contribute to the aggressive clinical characteristics of double-hit lymphoma (DHL). An effective therapy for DHL remains an unmet clinical need. In this study, we showed that both Ca2+ /calmodulin-dependent protein kinase II δ (CAMKIIδ) and γ (CAMKIIγ) were highly expressed in DHL. Both isoforms of CAMKII stabilize c-Myc protein by phosphorylating it at Ser62, increase BCL2 expression, and promote DHL tumor growth. Inhibition of CAMKIIδ and CAMKIIγ by either berbamine (BBM) or one of its derivatives (PA4) led to the down regulation of c-Myc and BCL2 proteins. BBM/PA4 also exhibited anti-tumor efficacy in DHL cell lines and NSG xenograft models. Altogether, CAMKIIδ and CAMKIIγ appear to be critical for DHL tumor development and are promising therapeutic targets for DHL.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfoma de Células B / Proteínas Proto-Oncogênicas c-myc / Linfoma Difuso de Grandes Células B / Proteínas Proto-Oncogênicas c-bcl-2 Idioma: En Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfoma de Células B / Proteínas Proto-Oncogênicas c-myc / Linfoma Difuso de Grandes Células B / Proteínas Proto-Oncogênicas c-bcl-2 Idioma: En Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China