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. 2023 Sep;37(9):1925-1928.
doi: 10.1038/s41375-023-01983-0. Epub 2023 Aug 2.

EZH2 targeting induces CD38 upregulation and response to anti-CD38 immunotherapies in multiple myeloma

Djamila Chemlal #  1   2 , Emmanuel Varlet #  2 , Amelie Machura  1 , Sara Ovejero  2   3 , Guilhem Requirand  3 , Nicolas Robert  3 , Guillaume Cartron  4   5 , Elina Alaterre  2 , Caroline Bret  2   3   5 , Laure Vincent  4 , Charles Herbaux  2   4   5 , Giacomo Cavalli  2 , Angélique Bruyer  1 , Hugues De Boussac  1 , Jerome Moreaux  6   7   8   9
Affiliations

EZH2 targeting induces CD38 upregulation and response to anti-CD38 immunotherapies in multiple myeloma

Djamila Chemlal et al. Leukemia. 2023 Sep.
No abstract available

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. CD38 expression is linked to EZH2 expression in MM cells.
A CD38 and EZH2 expression are significantly negatively correlated (p < 0.05) in CoMMpass cohort (n = 674). B EZH2 is significantly differentially expressed between the responder and the non-responder patients of a cohort of MM patients at relapse treated with Daratumumab (**p < 0.01) (n = 97). C CD38 mRNA expression is associated with enrichments of active (H3K4me3) or inactive (H3K27me3) histone marks on CD38 promoter (9 HMCLs, ChIP-seq experiments obtained as described [11]).
Fig. 2
Fig. 2. EPZ-6438 long term treatment improves anti-CD38 therapeutic antibodies efficacy in MM cells.
A 1 µM EPZ-6438 increases CD38 cell surface expression in 4 HMCLs at days 3, 6, and 9 (n = 3). B 9 days of 1 µM EPZ-6438 treatment improves ADCC induced by Daratumumab (Dara 1 µg/ml) and Isatuximab (Isa 1 µg/ml) in XG-20 CD38low MM cell line (Paired Student T-test, *p < 0.05; **p < 0.01). NK numbers represent the different blood samples from healthy donors used for NK cell isolation. C 12 days of EPZ-6438 treatment induces significant CD38 protein re-expression in primary MM samples (n = 5, p < 0.05 using paired Student T-test) (i). 12 days of 1 µM EPZ-6438 treatment improves MM cell lysis induced by 48 h of Daratumumab (Dara 1 µg/ml) treatment in eight primary MM bone marrow samples, including four collected at relapse after Daratumumab treatment (ii).
See this image and copyright information in PMC

References

    1. van de Donk N, Pawlyn C, Yong KL. Multiple myeloma. Lancet. 2021;397:410–27. doi: 10.1016/S0140-6736(21)00135-5. - DOI - PubMed
    1. Yamamoto C, Minakata D, Koyama S, Sekiguchi K, Fukui Y, Murahashi R, et al. Daratumumab in first-line therapy is cost-effective in transplant-eligible patients with newly diagnosed myeloma. Blood. 2022;140:594–607. doi: 10.1182/blood.2021015220. - DOI - PMC - PubMed
    1. Lee HC. Structure and enzymatic functions of human CD38. Mol Med. 2006;12:317–23. doi: 10.2119/2006-00086.Lee. - DOI - PMC - PubMed
    1. van de Donk NW, Janmaat ML, Mutis T, Lammerts van Bueren JJ, Ahmadi T, Sasser AK, et al. Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. Immunol Rev. 2016;270:95–112. doi: 10.1111/imr.12389. - DOI - PMC - PubMed
    1. Saltarella I, Desantis V, Melaccio A, Solimando AG, Lamanuzzi A, Ria R, et al. Mechanisms of resistance to anti-CD38 daratumumab in multiple myeloma. Cells. 2020;9:167. doi: 10.3390/cells9010167. - DOI - PMC - PubMed

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