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

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 (TP53 wt) HMCLs (p = 0.0029). Q-RT-PCR assays showed that TP73 was expressed in 57% of TP53 wt HMCLs (4 out of 7) and 11% of TP53 abnormal (TP53 abn) HMCLs (2 out of 18) (p = 0.0463). We showed that TP73 is silenced by methylation in TP53 abn HMCLs and that decitabine increased its expression, which, however, remained insufficient for significant protein expression. Alkylating drugs increased expression of TP73 only in TP53 wt HMCLs but failed to synergize with decitabine in TP53 abn HMCLs. (4) Conclusions: Decitabine and melphalan does not appear as a promising combination for inducing p73 and bypassing p53 deficiency in myeloma cells.
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Submitted on : Wednesday, January 24, 2018 - 9:08:33 AM
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Pierre-Samuel Gillardin, Géraldine Descamps, Sophie Maiga, Benoit Tessoulin, Hanane Djamai, et al.. Decitabine and Melphalan Fail to Reactivate p73 in p53 Deficient Myeloma Cells. International Journal of Molecular Sciences, MDPI, 2017, 19 (1), ⟨10.3390/ijms19010040⟩. ⟨inserm-01691503⟩



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