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Research Article

BRD4 PROTAC degrader MZ1 exhibits anti-B-cell acute lymphoblastic leukemia effects via targeting CCND3

Li Maa Department of Hematology, Children’s Hospital of Soochow University, Suzhou, People’s Republic of China;b Department of Pediatrics, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, People’s Republic of ChinaView further author information
,
Jianwei Wangc Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Yang Yangc Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Jun Lua Department of Hematology, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Jing Linga Department of Hematology, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Xinran Chua Department of Hematology, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Zimu Zhangc Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Yanfang Taoc Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Xiaolu Lic Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Yuanyuan Tiana Department of Hematology, Children’s Hospital of Soochow University, Suzhou, People’s Republic of China;c Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Zhiheng Lic Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Yongping Zhanga Department of Hematology, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Xu Sanga Department of Hematology, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Lihui Lua Department of Hematology, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Xiaomei Wana Department of Hematology, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Kunlong Zhanga Department of Hematology, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Yanling Chenc Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Juanjuan Yuc Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Ran Zhuoc Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Shuiyan Wud Intensive Care Unit, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Jian Panc Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Xiuxia Zhouc Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaView further author information
,
Yixin Hua Department of Hematology, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaCorrespondence[email protected] [email protected]
View further author information
&
Shaoyan Hua Department of Hematology, Children’s Hospital of Soochow University, Suzhou, People’s Republic of ChinaCorrespondence[email protected] [email protected]
View further author information
 show all
Article: 2247253 | Received 12 May 2023, Accepted 03 Aug 2023, Published online: 18 Aug 2023

References

  • Neerav Shukla MMLS, MD. Blinatumomab for treatment of children with high-risk relapsed B-cell acute lymphoblastic leukemia. JAMA. 2021;325(9):830–832.
  • Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.
  • Rajakumar SA, Papp E, Lee KK, et al. B cell acute lymphoblastic leukemia cells mediate RANK-RANKL–dependent bone destruction. Sci Transl Med. 2020;12(561):eaba5942.
  • Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33.
  • Zanetti C, Kumar R, Ender J, et al. The age of the bone marrow microenvironment influences B-cell acute lymphoblastic leukemia progression via CXCR5-CXCL13. Blood. 2021;138(19):1870–1884.
  • Stathis A, Bertoni F. Bet proteins as targets for anticancer treatment. Cancer Discov. 2018;8(1):24–36.
  • Belkina AC, Denis GV. BET domain co-regulators in obesity, inflammation and cancer. Nat Rev Cancer. 2012;12(7):465–477.
  • Filippakopoulos P, Knapp S. Targeting bromodomains: epigenetic readers of lysine acetylation. Nat Rev Drug Discovery. 2014;13(5):337–356.
  • Devaiah BN, Gegonne A, Singer DS. Bromodomain 4: a cellular Swiss army knife. J Leukocyte Biol. 2016;100(4):679–686.
  • Peirs S, Frismantas V, Matthijssens F, et al. Targeting BET proteins improves the therapeutic efficacy of BCL-2 inhibition in T-cell acute lymphoblastic leukemia. Leukemia. 2017;31(10):2037–2047.
  • Chaidos A, Caputo V, Karadimitris A. Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence. Ther Adv Hematol. 2015;6(3):128–141.
  • Andrieu GP, Kohn M, Simonin M, et al. PRC2 loss of function confers a targetable vulnerability to BET proteins in T-ALL. Blood. 2021;138(19):1855–1869.
  • Filippakopoulos P, Qi J, Picaud S, et al. Selective inhibition of BET bromodomains. Nature. 2010;468(7327):1067–1073.
  • Zuber J, Shi J, Wang E, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature. 2011;478(7370):524–528.
  • Li X, Song Y. Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy. J Hematol Oncol. 2020;13(1):50.
  • Lai AC, Toure M, Hellerschmied D, et al. Modular PROTAC design for the degradation of oncogenic BCR-ABL. Angew Chem, Int Ed. 2016;55(2):807–810.
  • Bondeson DP, Mares A, Smith IED, et al. Catalytic in vivo protein knockdown by small-molecule PROTACs. Nat Chem Biol. 2015;11(8):611–617.
  • Otto C, Schmidt S, Kastner C, et al. Targeting bromodomain-containing protein 4 (BRD4) inhibits MYC expression in colorectal cancer cells. Neoplasia. 2019;21(11):1110–1120.
  • Noblejas-López M, Nieto-Jimenez C, Burgos M, et al. Activity of BET-proteolysis targeting chimeric (PROTAC) compounds in triple negative breast cancer. J Exp Clin Cancer Res. 2019;38(1):383.
  • Ma L, Wang J, Zhang Y, et al. BRD4 PROTAC degrader MZ1 exerts anticancer effects in acute myeloid leukemia by targeting c-Myc and ANP32B genes. Cancer Biol Ther. 2022;23(1):1–15.
  • Devaiah BN, Singer DS. Two faces of brd4: mitotic bookmark and transcriptional lynchpin. Transcription. 2013;4(1):13–17.
  • Cooper AB, Sawai CM, Sicinska E, et al. A unique function for cyclin D3 in early B cell development. Nat Immunol. 2006;7(5):489–497.
  • Inaba H, Mullighan CG. Pediatric acute lymphoblastic leukemia. Haematologica. 2020;105(11):2524–2539.
  • Sanjuan-Pla A, Bueno C, Prieto C, et al. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia. Blood. 2015;126(25):2676–2685.
  • Ratti S, Lonetti A, Follo MY, et al. B-ALL complexity: is targeted therapy still a valuable approach for pediatric patients? Cancers (Basel). 2020;12(12)):3498.
  • Jabbour E, Pui C-H, Kantarjian H. Progress and innovations in the management of adult acute lymphoblastic leukemia. JAMA Oncol. 2018;4(10):1413–1420.
  • Lopez-Millan B, Sanchéz-Martínez D, Roca-Ho H, et al. NG2 antigen is a therapeutic target for MLL-rearranged B-cell acute lymphoblastic leukemia. Leukemia. 2019;33(7):1557–1569.
  • Knoechel B, Roderick JE, Williamson KE, et al. An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia. Nat Genet. 2014;46(4):364–370.
  • Latif A-L, Newcombe A, Li S, et al. BRD4-mediated repression of p53 is a target for combination therapy in AML. Nat Commun. 2021;12(1):241.
  • Peter B, Eisenwort G, Sadovnik I, et al. Brd4 degradation blocks expression of MYC and multiple forms of stem cell resistance in Ph+ chronic myeloid leukemia. Am J Hematol. 2022;97(9):1215–1225.
  • Ott CJ, Kopp N, Bird L, et al. BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012;120(14):2843–2852.
  • Li K, Crews CM. PROTACs: past, present and future. Chem Soc Rev. 2022;51(12):5214–5236.
  • Chi Y, Huang S, Liu M, et al. Cyclin D3 predicts disease-free survival in breast cancer. Cancer Cell Int. 2015;15(1)):89.
  • Pikman Y, Alexe G, Roti G, et al. Synergistic drug combinations with a CDK4/6 inhibitor in T-cell acute lymphoblastic leukemia. Clin Cancer Res. 2017;23(4):1012–1024.
  • Boldrin E, Gaffo E, Niedermayer A, et al. MicroRNA-497/195 is tumor suppressive and cooperates with CDKN2A/B in pediatric acute lymphoblastic leukemia. Blood. 2021;138(20):1953–1965.
  • Mao X, Liang S-b, Hurren R, et al. Cyproheptadine displays preclinical activity in myeloma and leukemia. Blood. 2008;112(3):760–769.
  • Martín-Garcia D, Navarro A, Valdés-Mas R, et al. CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1− mantle cell lymphoma. Blood. 2019;133(9):940–951.
  • Ketzer F, Abdelrasoul H, Vogel M, et al. CCND3 is indispensable for the maintenance of B-cell acute lymphoblastic leukemia. Oncogenesis. 2022;11(1):1.

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