A genome-scale CRISPR-Cas9 screening in myeloma cells identifies regulators of immunomodulatory drug sensitivity
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Immunomodulatory drugs (IMiDs) including lenalidomide and pomalidomide bind cereblon (CRBN) and activate the CRL4 CRBN ubiquitin ligase to trigger proteasomal degradation of the essential transcription factors IKZF1 and IKZF3 and multiple myeloma (MM) cytotoxicity. We have shown that CRBN is also targeted for degradation by SCF Fbxo7 ubiquitin ligase. In the current study, we explored the mechanisms underlying sensitivity of MM cells to IMiDs using genome-wide CRISPR-Cas9 screening. We validate that CSN9 signalosome complex, a deactivator of Cullin-RING ubiquitin ligase, inhibits SCF Fbxo7 E3 ligase-mediated CRBN degradation, thereby conferring sensitivity to IMiDs; conversely, loss of function of CSN9 signalosome activates SCF Fbxo7 complex, thereby enhancing degradation of CRBN and conferring IMiD resistance. Finally, we show that pretreatment with either proteasome inhibitors or NEDD8 activating enzyme (NAE) inhibitors can abrogate degradation and maintain levels of CRBN, thereby enhancing sensitivity to IMiDs. These studies therefore demonstrate that CSN9 signalosome complex regulates sensitivity to IMiDs by modulating CRBN expression.
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Several functional genomics campaigns have helped map how the repertoire of CRLs and their regulators shape degrader efficacy, outlining putative resistance mechanisms.
“Several functional genomics campaigns in recent years have helped map how the repertoire of CLRs and their regulators shape degrader efficacy, thus also outlining putative resistance mechanisms.141-151”
From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [144]
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Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339 · see citing works
RNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210 · see citing works
Improved vectors and genome-wide libraries for CRISPR screening
Sanjana, N. E., Shalem, O., & Zhang, F. (2014) · Nature Methods · doi:10.1038/nmeth.3047 · Cited by 5,239 · see citing works
Genome-scale CRISPR-Cas9 knockout screening in human cells
Shalem, O., Sanjana, N. E., Hartenian, E., Shi, X., Scott, D. A., Mikkelsen, T. S., Heckl, D., Ebert, B. L., Root, D. E., Doench, J. G., et al. (2014) · Science · doi:10.1126/science.1247005 · Cited by 5,234 · see citing works
Genetic screens in human cells using the CRISPR-Cas9 system
Wang, T., Wei, J. J., Sabatini, D. M., & Lander, E. S. (2014) · Science · doi:10.1126/science.1246981 · Cited by 2,856 · see citing works
Antitumor Activity of Thalidomide in Refractory Multiple Myeloma
Singhal, S., Mehta, J., Desikan, R., Ayers, D., Roberson, P., Eddlemon, P., Munshi, N., Anaissie, E., Wilson, C., Dhodapkar, M., et al. (1999) · New England Journal of Medicine · doi:10.1056/nejm199911183412102 · Cited by 2,575 · see citing works
Bortezomib or High-Dose Dexamethasone for Relapsed Multiple Myeloma
Richardson, P. G. G., Sonneveld, P., Schuster, M. W., Irwin, D. H., Stadtmauer, E. A., Facon, T. T. F., Harousseau, J., Ben‐Yehuda, D., Lonial, S., Goldschmidt, H., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043445 · Cited by 2,488 · see citing works
Self-citationPalumbo, A. P., & Anderson, K. C. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1011442 · Cited by 2,338 · see citing works
Self-citationRaje, N. S., & Anderson, K. C. (2000) · Current Treatment Options in Oncology · doi:10.1007/s11864-000-0017-x · Cited by 2,164 · see citing works
Self-citationIdentification of a Primary Target of Thalidomide Teratogenicity
Ito, T., Ando, H., Suzuki, T., Ogura, T., Hotta, K., Imamura, Y., Yamaguchi, Y., & Handa, H. (2010) · Science · doi:10.1126/science.1177319 · Cited by 2,136 · see citing works
An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer
Soucy, T. A., Smith, P. G., Milhollen, M. A., Berger, A. J., Gavin, J. M., Adhikari, S., Brownell, J. E., Burke, K. E., Cardin, D. P., Critchley, S., et al. (2009) · Nature · doi:10.1038/nature07884 · Cited by 1,990 · see citing works
Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells
Krönke, J., Udeshi, N. D., Narla, A., Grauman, P., Hurst, S. N., McConkey, M., Svinkina, T., Heckl, D., Comer, E., Li, X., et al. (2014) · Science · doi:10.1126/science.1244851 · Cited by 1,879 · see citing works
The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins
Lu, G., Middleton, R. E., Sun, H., Naniong, M., Ott, C. J., Mitsiades, C. S., Wong, K.-K., Bradner, J. E., & Kaelin, W. G. (2014) · Science · doi:10.1126/science.1244917 · Cited by 1,583 · see citing works
Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma
Lonial, S., Dimopoulos, M., Palumbo, A., White, D., Grosicki, S., Spicka, I., Walter-Croneck, A., Moreau, P., Mateos, M.-V., Magen, H., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1505654 · Cited by 1,322 · see citing works
Self-citationLenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma
Attal, M., Lauwers-Cances, V., Hulin, C., Leleu, X., Caillot, D., Escoffre, M., Arnulf, B., Macro, M., Belhadj, K., Garderet, L., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1611750 · Cited by 1,257 · see citing works
Self-citationLenalidomide after Stem-Cell Transplantation for Multiple Myeloma
McCarthy, P. L., Owzar, K., Hofmeister, C. C., Hurd, D. D., Hassoun, H., Richardson, P. G., Giralt, S., Stadtmauer, E. A., Weisdorf, D. J., Vij, R., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1114083 · Cited by 1,147 · see citing works
Self-citationStructure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide
Fischer, E. S., Böhm, K., Lydeard, J. R., Yang, H., Stadler, M. B., Cavadini, S., Nagel, J., Serluca, F., Acker, V., Lingaraju, G. M., et al. (2014) · Nature · doi:10.1038/nature13527 · Cited by 1,141 · see citing works
Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma
Lokhorst, H. M., Plesner, T., Laubach, J. P., Nahi, H., Gimsing, P., Hansson, M., Minnema, M. C., Lassen, U., Krejcik, J., Palumbo, A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1506348 · Cited by 1,117 · see citing works
Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets
Hideshima, T., Mitsiades, C., Tonon, G., Richardson, P. G., & Anderson, K. C. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2189 · Cited by 932 · see citing works
Self-citationLenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS
Krönke, J., Fink, E. C., Hollenbach, P. W., MacBeth, K. J., Hurst, S. N., Udeshi, N. D., Chamberlain, P. P., Mani, D. R., Man, H. W., Gandhi, A. K., et al. (2015) · Nature · doi:10.1038/nature14610 · Cited by 863 · see citing works
Multiple myeloma: evolving genetic events and host interactions
Kuehl, W. M., & Bergsagel, P. L. (2002) · Nature Reviews Cancer · doi:10.1038/nrc746 · Cited by 818 · see citing works
Lopez-Girona, A., Mendy, D., Ito, T., Miller, K., Gandhi, A. K., Kang, J., Karasawa, S., Carmel, G., Jackson, P., Abbasian, M., et al. (2012) · Leukemia · doi:10.1038/leu.2012.119 · Cited by 814 · see citing works
Promotion of NEDD8-CUL1 Conjugate Cleavage by COP9 Signalosome
Lyapina, S., Cope, G. A., Shevchenko, A., Serino, G., Tsuge, T., Zhou, C., Wolf, D. A., Wei, N., Shevchenko, A., & Deshaies, R. J. (2001) · Science · doi:10.1126/science.1059780 · Cited by 699 · see citing works
Mechanisms and function of substrate recruitment by F-box proteins
Skaar, J. R., Pagan, J. K., & Pagano, M. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3582 · Cited by 671 · see citing works
Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase
Petzold, G., Fischer, E. S., & Thomä, N. H. (2016) · Nature · doi:10.1038/nature16979 · Cited by 620 · see citing works
Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide
Zhu, Y. X., Braggio, E., Shi, C.-X., Bruins, L. A., Schmidt, J. E., Van Wier, S., Chang, X.-B., Bjorklund, C. C., Fonseca, R., Bergsagel, P. L., et al. (2011) · Blood · doi:10.1182/blood-2011-05-356063 · Cited by 607 · see citing works
Fermand, J.-P., Ravaud, P., Chevret, S., Divine, M., Leblond, V., Belanger, C., Macro, M., Pertuiset, E., Dreyfus, F., Mariette, X., et al. (1998) · Blood · doi:10.1182/blood.v92.9.3131 · Cited by 542 · see citing works
Chamberlain, P. P., Lopez-Girona, A., Miller, K., Carmel, G., Pagarigan, B., Chie-Leon, B., Rychak, E., Corral, L. G., Ren, Y. J., Wang, M., et al. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2874 · Cited by 531 · see citing works
Cope, G. A., & Deshaies, R. J. (2003) · Cell · doi:10.1016/s0092-8674(03)00722-0 · Cited by 409 · see citing works
The proteasome and proteasome inhibitors in multiple myeloma
Gandolfi, S., Laubach, J. P., Hideshima, T., Chauhan, D., Anderson, K. C., & Richardson, P. G. G. (2017) · Cancer and Metastasis Reviews · doi:10.1007/s10555-017-9707-8 · Cited by 342 · see citing works
Self-citationPomalidomide (CC4047) Plus Low-Dose Dexamethasone As Therapy for Relapsed Multiple Myeloma
Lacy, M. Q., Hayman, S. R., Gertz, M. A., Dispenzieri, A., Buadi, F., Kumar, S., Greipp, P. R., Lust, J. A., Russell, S. J., Dingli, D., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.23.6802 · Cited by 317 · see citing works
Lenhoff, S., Hjorth, M., Holmberg, E. C., Turesson, I., Westin, J., Nielsen, J. L., Wislöff, F., Brinch, L., Carlson, K. E., Carlsson, M. S., et al. (2000) · PubMed · doi:10.1182/blood.v95.1.7 · Cited by 310 · see citing works
Panobinostat for the Treatment of Multiple Myeloma
Laubach, J. P., Moreau, P., Miguel, J. F. S., & Richardson, P. G. G. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0530 · Cited by 260 · see citing works
A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation
Higgins, J. J., Pucilowska, J., Lombardi, R. Q., & Rooney, J. P. (2004) · Neurology · doi:10.1212/01.wnl.0000146196.01316.a2 · Cited by 250 · see citing works
U.S. Food and Drug Administration Approval: Carfilzomib for the Treatment of Multiple Myeloma
Herndon, T. M., Deisseroth, A., Kaminskas, E., Kane, R. C., Koti, K. M., Rothmann, M. D., Habtemariam, B. A., Bullock, J. M., Bray, J. D., Hawes, J. J., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0755 · Cited by 243 · see citing works
Crystal structure of the human COP9 signalosome
Lingaraju, G. M., Bunker, R. D., Cavadini, S., Heß, D., Hassiepen, U., Renatus, M., Fischer, E. S., & Thomä, N. H. (2014) · Nature · doi:10.1038/nature13566 · Cited by 231 · see citing works
Novel therapies targeting the myeloma cell and its bone marrow microenvironment
Hideshima, T., Chauhan, D., Podar, K., Schlossman, R. L., Richardson, P., & Anderson, K. C. (2001) · Seminars in Oncology · doi:10.1016/s0093-7754(01)90033-8 · Cited by 201 · see citing works
Self-citationRichardson, P. G. G., Xie, W., Jagannath, S., Jakubowiak, A. J., Lonial, S., Raje, N. S., Alsina, M., Ghobrial, I. M., Schlossman, R. L., Munshi, N. C., et al. (2014) · Blood · doi:10.1182/blood-2013-07-517276 · Cited by 180 · see citing works
Self-citationIxazomib: First Global Approval
Shirley, M. (2016) · Drugs · doi:10.1007/s40265-016-0548-5 · Cited by 170 · see citing works
Fermand, J., Lévy, Y., Gerota, J., Benbunan, M., Cosset, J. M., Castaigné, S., Seligmann, M., & Brouet, J. C. (1989) · Blood · doi:10.1182/blood.v73.1.20.20 · Cited by 151 · see citing works
Roles of COP9 signalosome in cancer
Lee, M., Zhao, R., Phan, L. M., & Yeung, S. J. (2011) · Cell Cycle · doi:10.4161/cc.10.18.17320 · Cited by 137 · see citing works
Daratumumab: First Global Approval
McKeage, K. (2016) · Drugs · doi:10.1007/s40265-015-0536-1 · Cited by 120 · see citing works
CRL4ACRBN E3 ubiquitin ligase restricts BK channel activity and prevents epileptogenesis
Liu, J., Ye, J., Zou, X., Xu, Z., Feng, Y., Zou, X., Chen, Z., Li, Y., & Cang, Y. (2014) · Nature Communications · doi:10.1038/ncomms4924 · Cited by 92 · see citing works
Self-citationOlma, M. H., Roy, M. M., Bihan, T. L., Sumara, I., Maerki, S., Larsen, B. G., Quadroni, M., Peter, M., Tyers, M., & Pintard, L. (2009) · Journal of Cell Science · doi:10.1242/jcs.043539 · Cited by 83 · see citing works
Diversity of COP9 signalosome structures and functional consequences
Dubiel, D., Rockel, B., Naumann, M., & Dubiel, W. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.06.007 · Cited by 66 · see citing works
Lee, E. K., & Diehl, J. A. (2013) · Oncogene · doi:10.1038/onc.2013.144 · Cited by 62 · see citing works
Chen, Y.-A., Peng, Y.-J., Hu, M.-C., Huang, J.-J., Chien, Y.-C., Wu, J.-T., Chen, T.-Y., & Tang, C.-Y. (2015) · Scientific Reports · doi:10.1038/srep10667 · Cited by 61 · see citing works
Hideshima, T., Cottini, F., Nozawa, Y., Seo, H., Ohguchi, H., Samur, M., Cirstea, D. D., Mimura, N., Iwasawa, Y., Richardson, P. G. G., et al. (2017) · Blood · doi:10.1182/blood-2016-09-738500 · Cited by 53 · see citing works
Self-citationSong, T., Liang, S., Liu, J., Zhang, T., Yin, Y., Geng, C., Gao, S., Feng, Y., Xu, H., Guo, D., et al. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007165 · Cited by 30 · see citing works
Self-citationCurrent Treatment for Multiple Myeloma
Avigan, D., & Rosenblatt, J. M. (2014) · New England Journal of Medicine · doi:10.1056/nejme1407442 · Cited by 26 · see citing works
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Mayor-Ruiz, C., Jaeger, M. G., Bauer, S., Brand, M., Sin, C., Hanzl, A., Mueller, A. C., Menche, J., & Winter, G. E. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.07.013 · Cited by 119 · see citing works
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Liang, Q., Tang, C., Tang, M., Zhang, Q., Gao, Y., & Ge, Z. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1143-x · Cited by 118 · see citing works
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Zhang, S. (2021) · Seminars in Oncology · doi:10.1053/j.seminoncol.2021.09.004 · Cited by 113 · see citing works
E1 Enzymes as Therapeutic Targets in Cancer
Barghout, S. H., & Schimmer, A. D. (2020) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000053 · Cited by 108 · see citing works
Ogiya, D., Liu, J., Ohguchi, H., Kurata, K., Samur, M. K., Tai, Y.-T., Adamia, S., Ando, K., Hideshima, T., & Anderson, K. C. (2020) · Blood · doi:10.1182/blood.2019004332 · Cited by 92 · see citing works
Self-citationEmerging roles of F-box proteins in cancer drug resistance
Yan, L., Lin, M., Pan, S., Assaraf, Y. G., Wang, Z. P., & Zhu, X. (2019) · Drug Resistance Updates · doi:10.1016/j.drup.2019.100673 · Cited by 85 · see citing works
PIKES Analysis Reveals Response to Degraders and Key Regulatory Mechanisms of the CRL4 Network
Reichermeier, K. M., Straube, R., Reitsma, J. M., Sweredoski, M. J., Rose, C. M., Moradian, A., den Besten, W., Hinkle, T., Verschueren, E., Petzold, G., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2019.12.013 · Cited by 78 · see citing works
Molecular mechanisms of cereblon-based drugs
Asatsuma‐Okumura, T., Ito, T., & Handa, H. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.06.004 · Cited by 77 · see citing works
CRISPR/Cas: From Tumor Gene Editing to T Cell-Based Immunotherapy of Cancer
Azangou‐Khyavy, M., Ghasemi, M., Khanali, J., Boroomand-Saboor, M., Jamalkhah, M., Soleimani, M., & Kiani, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02062 · Cited by 77 · see citing works
Ng, Y. L. D., Ramberger, E., Bohl, S., Dolnik, A., Steinebach, C., Conrad, T., Müller, S., Popp, O., Kull, M., Haji, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28515-1 · Cited by 68 · see citing works
Sperling, A. S., Burgess, M. W., Keshishian, H., Gasser, J. A., Bhatt, S., Jan, M., Slabicki, M. M., Sellar, R. S., Fink, E. C., Miller, P. G., et al. (2019) · Blood · doi:10.1182/blood.2019000789 · Cited by 65 · see citing works
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Davis, L. N., & Sherbenou, D. W. (2021) · Cancers · doi:10.3390/cancers13071686 · Cited by 61 · see citing works
Harding, T., Baughn, L. B., Kumar, S. K., & Ness, B. V. (2019) · Leukemia · doi:10.1038/s41375-018-0362-z · Cited by 54 · see citing works
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Fuchs, O. (2023) · Blood Reviews · doi:10.1016/j.blre.2022.100994 · Cited by 55 · see citing works
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Cippitelli, M., Stabile, H., Kosta, A., Petillo, S., Gismondi, A., Santoni, A., & Fionda, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031103 · Cited by 42 · see citing works
Identification and selectivity profiling of small-molecule degraders via multi-omics approaches
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Wang, L., Chen, Y., Liu, X., Li, Z., & Dai, X. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.704999 · Cited by 31 · see citing works
Patil, A., Manzano, M., & Gottwein, E. (2019) · Blood Advances · doi:10.1182/bloodadvances.2019031732 · Cited by 29 · see citing works
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Mogollón, P., Díaz-Tejedor, A., Algarín, E. M., Paíno, T., Garayoa, M., & Ocio, E. M. (2019) · Cells · doi:10.3390/cells8111432 · Cited by 30 · see citing works
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Hosseini, S. A., Jouneghani, A. S., Ghatrehsamani, M., Yaghoobi, H., Elahian, F., & Mirzaei, S. A. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.11.018 · Cited by 27 · see citing works
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Maura, F., Landgren, O., & Morgan, G. J. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-1395 · Cited by 26 · see citing works
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Self-citationKulig, P., Milczarek, S., Bakinowska, E., Szalewska, L., Baumert, B., & Machaliński, B. (2023) · Cancers · doi:10.3390/cancers15030963 · Cited by 26 · see citing works
Chen, J., Shi, J., Shao, H., Li, B., Ji, T., Staiculescu, D., He, J., Zhao, J., Cai, L., Liang, X. H., et al. (2022) · Science China Life Sciences · doi:10.1007/s11427-021-2067-7 · Cited by 24 · see citing works
Li, P., Hu, X., Fan, Z., Sun, S., Ran, Q., Wei, T., Wei, P., Jiang, Q., Yan, J. W., Yang, N., et al. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01592-z · Cited by 24 · see citing works
Jones, J. R., Barber, A., Bihan, Y. L., Weinhold, N., Ashby, C., Walker, B. A., Wardell, C. P., Wang, H., Kaiser, M., Jackson, G. H., et al. (2021) · Leukemia · doi:10.1038/s41375-021-01373-4 · Cited by 23 · see citing works
Loss of COP9 signalosome genes at 2q37 is associated with IMiD resistance in multiple myeloma
Gooding, S., Ansari‐Pour, N., Kazeroun, M. H., Karagoz, K., Polonskaia, A., Salazar, M. A., Fitzsimons, E., Sirinukunwattana, K., Chavda, S. J., Estévez, M. O., et al. (2022) · Blood · doi:10.1182/blood.2022015909 · Cited by 23 · see citing works
Deciphering the mechanisms of CC-122 resistance in DLBCL via a genome-wide CRISPR screen
Mo, Z., Wood, S., Namiranian, S., Mizukoshi, R., Weng, S., Jang, I. S., Fontanillo, C., Baughman, J. M., Silva-Torres, A., Slade, M., et al. (2021) · Blood Advances · doi:10.1182/bloodadvances.2020003431 · Cited by 21 · see citing works
Bohl, S., Schmalbrock, L. K., Bauhuf, I., Meyer, T., Dolnik, A., Szyska, M., Blätte, T. J., Knödler, S., Röhner, L., Miller, D., et al. (2021) · Blood Advances · doi:10.1182/bloodadvances.2020003541 · Cited by 19 · see citing works
Wirth, A.-K., Wange, L. E., Vosberg, S., Henrich, K., Rausch, C. R., Özdemir, E. Z., Zeller, C., Richter, D., Feuchtinger, T. F., Kaller, M., et al. (2022) · Leukemia · doi:10.1038/s41375-022-01726-7 · Cited by 18 · see citing works
Niu, Y., Fan, X., Wang, Y.-P., Lin, J., Hua, L., Li, X., Qian, R., & Lü, C. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.949715 · Cited by 18 · see citing works
Key regulators of sensitivity to immunomodulatory drugs in cancer treatment
Wang, S., Li, Z., & Gao, S. (2021) · Biomarker Research · doi:10.1186/s40364-021-00297-6 · Cited by 17 · see citing works
Self-citationZhou, L., & Xu, G. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167457 · Cited by 17 · see citing works
High-Throughput CRISPR Screening in Hematological Neoplasms
Ancos-Pintado, R., Bragado-García, I., Morales, M. L., García-Vicente, R., Arroyo-Barea, A., Rodríguez-García, A., Martínez-López, J., Linares, M., & Hernández-Sánchez, M. (2022) · Cancers · doi:10.3390/cancers14153612 · Cited by 15 · see citing works
Tumor and microenvironmental mechanisms of resistance to immunomodulatory drugs in multiple myeloma
Chen, L., & Gooding, S. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1038329 · Cited by 12 · see citing works
Applying CRISPR-Cas9 screens to dissect hematological malignancies
Iyer, D. N., Schimmer, A. D., & Chang, H. (2022) · Blood Advances · doi:10.1182/bloodadvances.2022008966 · Cited by 10 · see citing works
Aubry, A., Pearson, J. D., Charish, J., Tao, Y., Sivak, J. M., Xirodimas, D. P., Avet‐Loiseau, H., Corre, J., Monnier, P. P., & Bremner, R. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112925 · Cited by 10 · see citing works
Targeting the ubiquitin pathway in lymphoid malignancies
Li, B., Eichhorn, P. J. A., & Chng, W. J. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216978 · Cited by 10 · see citing works
Wang, B., Duan, J., & Zhou, L. (2021) · Anti-Cancer Drugs · doi:10.1097/cad.0000000000001041 · Cited by 10 · see citing works
Hu, S., Xu, J., Cui, W., Jin, H.-R., Wang, X., & Maimaitiyiming, Y. (2025) · Biomolecules · doi:10.3390/biom15050702 · Cited by 9 · see citing works
Mapping the IM i D ‐dependent cereblon interactome using B io ID ‐proximity labelling
Costacurta, M., Sandow, J. J., Maher, B. M., Susanto, O., Vervoort, S. J., Devlin, J. R., Garama, D. J., Condina, M. R., Steele, J. R., Kahrood, H. V., et al. (2024) · FEBS Journal · doi:10.1111/febs.17196 · Cited by 9 · see citing works
Zhou, L., Yu, W.-J., Jayabalan, D. S., Niesvizky, R., Jaffrey, S. R., Huang, X., & Xu, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.605989 · Cited by 9 · see citing works
Wang, B., Li, M., Cao, D., Sun, Q., Yu, W.-J., Ma, J., Ren, H., Xu, G., & Zhou, L. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05390-1 · Cited by 8 · see citing works
Costacurta, M., Vervoort, S. J., Hogg, S. J., Martin, B. P., Johnstone, R. W., & Shortt, J. (2020) · Haematologica · doi:10.3324/haematol.2020.265611 · Cited by 8 · see citing works
Manni, S., Fregnani, A., Barilà, G., Zambello, R., Semenzato, G., & Piazza, F. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00802 · Cited by 7 · see citing works
Caspase-8: Friend or Foe in Bortezomib/Lenalidomide-Based Therapy for Myeloma
Zhou, L. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.861709 · Cited by 7 · see citing works
Wu, J., Chu, E., Paul, B. A., & Kang, Y. (2022) · Cancers · doi:10.3390/cancers14215272 · Cited by 7 · see citing works
Methods to characterize and discover molecular degraders in cells
Lin, Z., & Woo, C. M. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00261b · Cited by 6 · see citing works
CRISPR-based precision medicine for hematologic disorders: Advancements, challenges, and prospects
Sahu, S., Poplawska, M., Lim, S. H., & Dutta, D. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122165 · Cited by 9 · see citing works
Kdm4a is an activity downregulated barrier to generate engrams for memory separation
Guo, X., Hong, P., Xiong, S., Yan, Y., Xie, H. B., & Guan, J. (2024) · Nature Communications · doi:10.1038/s41467-024-50218-y · Cited by 6 · see citing works
He, Y., Li, H., Ju, X., & Gong, B. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2024.189212 · Cited by 6 · see citing works
Cereblon-Targeting Ligase Degraders in Myeloma
Lee, H., Neri, P. E., & Bahlis, N. J. (2024) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2024.01.001 · Cited by 5 · see citing works
Therapeutic status and the prospect of CRISPR/Cas9 gene editing in multiple myeloma
Hong, L., Zhang, C., Jiang, Y., Liu, H., Huang, H., & Guo, D. (2020) · Future Oncology · doi:10.2217/fon-2019-0822 · Cited by 5 · see citing works
Rosell, R., Filipska, M., CHAIB-OUKADOUR, I., Lligé, D., & Laguía, F. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01726 · Cited by 5 · see citing works
Zou, L., Cao, D., Sun, Q. P., Yu, W.-J., Li, B.-Z., Xu, G., & Zhou, L. (2025) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-025-00697-8 · Cited by 5 · see citing works
Qiu, M., Zhang, Q., Li, R., Wei, R., Zhao, J., Tan, J., Zhang, H., & Qiao, W. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02702-7 · Cited by 3 · see citing works
Barbosa, B. M. G., Sfyaki, A., Rafael, S., José‐Duran, F., Pous, J., Sánchez, C., Perez‐Lopez, C., Vilanova, M., Cigler, M., Gay, M., et al. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202316730 · Cited by 3 · see citing works
Barbosa, B. M. G., Sfyaki, A., Rafael, S., José‐Duran, F., Pous, J., Sánchez, C., Perez‐Lopez, C., Vilanova, M., Cigler, M., Gay, M., et al. (2023) · Angewandte Chemie · doi:10.1002/ange.202316730 · Cited by 2 · see citing works
Increased CSN5 expression enhances the sensitivity to lenalidomide in multiple myeloma cells
Yamamoto, T., Furukawa, A., Zhou, Y., Kono, N., Kitajima, S., Ohguchi, H., Kawano, Y., Ito, S., Araki, N., Ohtsuki, S., et al. (2024) · iScience · doi:10.1016/j.isci.2024.111399 · Cited by 1 · see citing works
Liu, Y., Sun, Y., Song, T.-Y., Ni, S.-Y., Pu, Y.-S., Chang, Y. H., Zhou, W.-X., Peng, Z.-G., Liu, J., Shi, J., et al. (2026) · Cancer Research · doi:10.1158/0008-5472.can-25-3941 · Cited by 1 · see citing works
Self-citationThe synthetic landscape of cereblon (CRBN) binders: from thalidomide to emerging chemotypes
Rafael, S., Sánchez, C., Whelan, R., Harris, C., Verdaguer, X., Mayor‐Ruiz, C., & Riéra, A. (2026) · Chemical Society Reviews · doi:10.1039/d6cs00247a · Cited by 1 · see citing works
What Is Genomic High-Risk Myeloma?
Davies, F. E., & Walker, B. A. (2022) · Hemato · doi:10.3390/hemato3020021 · Cited by 1 · see citing works
Suzuki, K., & Yano, S. (2023) · Life · doi:10.3390/life13112229 · Cited by 1 · see citing works
Barghout, S. H. (2020) · TSpace (University of Toronto) · doi:10.13140/rg.2.2.10284.90246 · Cited by 1 · see citing works
History of IMiDs and Protein Degradation as a Pharmacological Modality
Yamamoto, J., Asatsuma‐Okumura, T., Ito, T., Yamaguchi, Y., & Handa, H. (2022) · Wiley eBooks · doi:10.1002/9781119774198.ch8 · Cited by 1 · see citing works
Targeted KRAS G12V degradation elicits efficient and durable lung adenocarcinoma regression in vivoPreprint
Martín, A. J. M., García-Pérez, I. M., José, S. S., Rojo, P., Riego‐Mejías, C., Teodósio, C., Barbosa, B. M. G., Sánchez, C., Folch-I-Casanovas, I., Caballol, A. O., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.13.627539 · Cited by 1 · see citing works
Maura, F., Landgren, O., & Morgan, G. J. (2023) · doi:10.1158/1078-0432.c.6530273
Maura, F., Landgren, O., & Morgan, G. J. (2023) · doi:10.1158/1078-0432.c.6530273.v1
Heterobifunctional Degraders for the Treatment of Lymphoid Malignancies
Gollerkeri, A. M., Gollob, A. J., & Mainolfi, N. (2023) · doi:10.1002/9781119819950.ch26
Epigenetic regulation of Cereblon in cancer: molecular mechanisms and clinical implications
Yi, J. M. (2025) · Genes & Genomics · doi:10.1007/s13258-025-01689-w
North, D. L., Meaker, G. A., & Khan, A. O. (2026) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2026.02.018
Li, H., Xia, Q., Yu, M., Lv, Y., Xiao, J., Guo, X., Dong, K., Zhou, Y., Zhong, L., Wang, T., et al. (2026) · Science China Life Sciences · doi:10.1007/s11427-025-3227-0
CRISPR application in hematological disorders: from bench to bedside
Ladisa, F., Morelli, E., Soncini, D., Garibotto, M., Munshi, N. C., Fulciniti, M., & Cea, M. (2026) · Blood Advances · doi:10.1182/bloodadvances.2025017417
- Authors
- Liu, J., Song, T., Zhou, W., Xing, L., Wang, S., Ho, M., Peng, Z., Tai, Y.-T., Hideshima, T., Anderson, K. C., & Cang, Y.
- Affiliations
- Harvard University (US)
- ShanghaiTech University (CN)
- WuXi AppTec (China) (CN)
- Corresponding author
- Anderson, Kenneth C.
- Cang, Yong
- ORCID
- Venue
- Leukemia
- Published
- 2018-07-19
- Volume
- 33
- Issue
- 1
- Pages
- 171-180
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- PMC
- PMC6475089
- OpenAlex
- W2883654450
- Cited by
- 83
- References
- 50
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 10 · 2023: 10 · 2022: 20 · 2021: 14 · 2020: 12 · 2019: 8
- FWCI
- 6.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Leukemia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p01ca078378-15, 5r01ca178264-05)
- National Cancer Institute (R01-CA178264, P01-CA078378, P50CA100707, R01CA050947, R01CA207237, P01CA155258)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- multiple myeloma, immunomodulators, lenalidomide, pomalidomide, cereblon, drug sensitivity, drug resistance, proteasome inhibitors, NEDD8-activating enzyme inhibitor, IKZF1, IKZF3
- MeSH terms
- Bortezomib, COP9 Signalosome Complex, Antineoplastic Agents, Cyclopentanes, Enzyme Inhibitors, Humans, Immunologic Factors, Multiple Myeloma, Peptide Hydrolases, Prognosis, Pyrimidines, Tumor Cells, Cultured, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Ubiquitin-Protein Ligases, Adaptor Proteins, Signal Transducing, Ikaros Transcription Factor, Ubiquitination, Proteolysis, CRISPR-Cas Systems
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