IJMS, Vol. 19, Pages 40: Decitabine and Melphalan Fail to Reactivate p73 in p53 Deficient Myeloma Cells

IJMS, Vol. 19, Pages 40: Decitabine and Melphalan Fail to Reactivate p73 in p53 Deficient Myeloma Cells

International Journal of Molecular Sciences doi: 10.3390/ijms19010040

Authors: Pierre-Samuel Gillardin Géraldine Descamps Sophie Maiga Benoit Tessoulin Hanane Djamai Benedetta Lucani David Chiron Philippe Moreau Steven Le Gouill Martine Amiot Catherine Pellat-Deceunynck Agnès Moreau-Aubry

(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.

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