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Int. J. Mol. Sci. 2018, 19(1), 40; https://doi.org/10.3390/ijms19010040

Decitabine and Melphalan Fail to Reactivate p73 in p53 Deficient Myeloma Cells

1
CRCINA, INSERM, CNRS, Université d’Angers, Université de Nantes, 44007 Nantes, France
2
Service d’Hématologie Clinique, Unité d’Investigation Clinique, CHU, 44093 Nantes, France
*
Author to whom correspondence should be addressed.
Received: 25 November 2017 / Revised: 20 December 2017 / Accepted: 22 December 2017 / Published: 23 December 2017
(This article belongs to the Special Issue Novel Therapeutic Strategies in Multiple Myeloma)
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Abstract

(1) Background: TP53 deficiency remains a major adverse event in Multiple Myeloma (MM) despite therapeutic progresses. As it is not possible to target TP53 deficiency with pharmacological agents, we explored the possibility of activating another p53 family member, p73, which has not been well studied in myeloma. (2) Methods: Using human myeloma cell lines (HMCLs) with normal or abnormal TP53 status, we assessed TP73 methylation and expression. (3) Results: Using microarray data, we reported that TP73 is weakly expressed in 47 HMCLs and mostly in TP53 wild type (TP53wt) HMCLs (p = 0.0029). Q-RT-PCR assays showed that TP73 was expressed in 57% of TP53wt HMCLs (4 out of 7) and 11% of TP53 abnormal (TP53abn) HMCLs (2 out of 18) (p = 0.0463). We showed that TP73 is silenced by methylation in TP53abn HMCLs and that decitabine increased its expression, which, however, remained insufficient for significant protein expression. Alkylating drugs increased expression of TP73 only in TP53wt HMCLs but failed to synergize with decitabine in TP53abn HMCLs. (4) Conclusions: Decitabine and melphalan does not appear as a promising combination for inducing p73 and bypassing p53 deficiency in myeloma cells. View Full-Text
Keywords: multiple myeloma; p53; p73; CpG methylation; decitabine; alkylating drugs multiple myeloma; p53; p73; CpG methylation; decitabine; alkylating drugs
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Gillardin, P.-S.; Descamps, G.; Maiga, S.; Tessoulin, B.; Djamai, H.; Lucani, B.; Chiron, D.; Moreau, P.; Le Gouill, S.; Amiot, M.; Pellat-Deceunynck, C.; Moreau-Aubry, A. Decitabine and Melphalan Fail to Reactivate p73 in p53 Deficient Myeloma Cells. Int. J. Mol. Sci. 2018, 19, 40.

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