title: PRIMA-1Met induces apoptosis in Waldenström's Macroglobulinemia cells independent of p53.
abstract: PRIMA-1Met has shown promising preclinical activity in various cancer types. However, its effect on Waldenström's Macroglobulinemia (WM) cells as well as its exact mechanism of action is still elusive. In this study, we evaluated the anti- tumor activity of PRIMA-1Met alone and in combination with dexamethasone or bortezomib in WM cell lines and primary samples. Treatment of WM cells with PRIMA-1Met resulted in induction of apoptosis, inhibition of migration and suppression of colony formation. Upon PRIMA-1Met treatment, p73 was upregulated and Bcl-xL was down-regulated while no significant change in expression of p53 was observed. Furthermore, siRNA knockdown of p53 in WM cell line did not influence the PRIMA-1Met-induced apoptotic response whereas silencing of p73 inhibited latter response in WM cells. Importantly, combined treatment of BCWM-1 cells with PRIMA-1Met and dexamethasone or bortezomib induced synergistic reduction in cell survival. Our study provides insights into the mechanisms of anti-WM activity of PRIMA-1Met and supports further clinical evaluation of PRIMA-1Met as a potential novel therapeutic intervention in WM.
authors: a Division of Molecular and Cellular Biology; Toronto General Hospital Research Institute ; Toronto , Ontario , Canada.
authors: Mona
authors: M
authors: Sobhani
authors: Jahangir
authors: J
authors: Abdi
authors: Saha N
authors: SN
authors: Manujendra
authors: Christine
authors: C
authors: Chen
authors: Hong
authors: H
authors: Chang
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D006801:Humans; D011812:Quinuclidines / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy*
chemical_list: D011812:Quinuclidines; D016159:Tumor Suppressor Protein p53; C533410:eprenetapopt
keywords: AML, acute myeloid Leukemia; BMMCs, bone marrow mononuclear cells.; CLL, chronic lymphocytic leukemia; MM, (Multiple Myeloma ); PBMCs, peripheral blood mononuclear cells; PRIMA-1Met; PRIMA-1Met, methylated P53 Reactivation and Induction of Massive Apoptosis; WM, (Waldenström's Macroglobulinemia); Waldenström's Macroglobulinemia; apoptosis; dexamethasone or bortezomib; p53; p73