EXPRESSION OF P73 IN MYELOMA CELL LINES AND PLASMA CELLS OF MULTIPLE MYELOMA PATIENTS

Background: Multiple myeloma (MM) Is a B-cell malignancy characterised by the accumulation of clonal plasma cells in the bone marrow. Myeloma biology is heterogeneous and this lead to a different clinical behavior. As for other type of cancers, hypermethylation could be a mechanism of resistance in myeloma. Hence, DNA methylation of p73 tumor-suppressor gene can potentially be biomarker for diagnosis or relapse in MM. Aim: The goal of this study was to identify the expression of p73 in myeloma evaluating it in 24 different myeloma cell lines and in multiple myeloma patients. Methods: we evaluated the expression of p73 by q-PCR in 24 HMCL and 6 patients, 2 with MGUS, 2 with MM at diagnosis and 2 with relapsed/refractory MM. We tested the expression of p73 in some HMCL, one per category, by western blot. Moreover, we analyzed the expression of p73 before and after treatment with 5- aza-2-deoxycytidine. Results: 14/21 HMCL (66.7%) did not express p73 to a significant level, 4/21 (19%) have been shown to express the gene and its encoded protein to low levels and only 3/21 (14.3%) expressed p73 to an intermediate level. By western blot, we observed that the protein has a very low concentration in all three categories, considered unexpressed. We have observed that 6/12 (50%) cell lines treated increased the expression of the gene p73 after treatment with 5-aza-2- deoxycytidine, but is not reflected in increasing production of the protein detected by western blot. Finally, we observed that 2/6 (33%) patients expressed the gene at low level and 4/6 (67%) patients did not express p73. Conclusions: Our data do not provide evidence that the expression of p73 may be useful as prognostic indicators at MM diagnosis, because our study is limited to few patients tested. To better define and assess the clinical impact of the p73 expression in MM, it is therefore necessary to test the expression of p73 also in a larger number of patient samples with multiple myeloma. This knowledge may help to develop new markers for detection of minimal residual disease and determine candidate patients for epigenetically targeted salvage therapy regimens.