Data from Targeting of BCL2 Family Proteins with ABT-199 and Homoharringtonine Reveals BCL2- and MCL1-Dependent Subgroups of Diffuse Large B-Cell Lymphoma

• DOI: 10.1158/1078-0432.c.6523509.v1
• Publication Date: 2023-04-01T06:40:45Z
• Authors: Magdalena Klanova; Ladislav Andera; Jan Brazina; Jan Svadlenka; Simona Benesova; Jan Soukup; Dana Prukova; Dana Vejmelkova; Radek Jaksa; Karel Helman; Petra Vockova; Lucie Lateckova; Jan Molinsky; Bokang Calvin Len...; Mahmudul Alam; Roman Kodet; Robert Pytlik; Marek Trneny; Pavel Klener
• Keywords: MCL1; Homoharringtonine; B-cell lymphoma; Immunoprecipitation

<div>Abstract<p><b>Purpose:</b> To investigate the roles of BCL2, MCL1, and BCL-XL in survival diffuse large B-cell lymphoma (DLBCL).</p><p><b>Experimental designs:</b> Immunohistochemical analysis 105 primary DLBCL samples, Western blot 18 cell lines for expression BCL-XL. Pharmacologic targeting with ABT-199, homoharringtonine (HHT), ABT-737. Analysis clones manipulated expressions Immunoprecipitation MCL1 complexes selected lines. Experimental therapy aimed at inhibition BCL2 using ABT-199 HHT, single agent, or combination, <i>in vitro</i> vivo</i> on cell-based murine xenograft models DLBCL.</p><p><b>Results:</b> By pharmacologic BCL-XL, we demonstrated that can be divided into BCL2-dependent MCL1-dependent subgroups a less pronounced role left Derived as well immunoprecipitation experiments, which analyzed protein complexes, confirmed these findings molecular level. We concurrent HHT induced significant synthetic lethality most BCL2-expressing The marked cytotoxic synergy between was also DLBCL.</p><p><b>Conclusions:</b> As is clinically approved antileukemia drug, advanced phases diverse clinical trials, our data might have direct implications novel concepts early trials patients aggressive DLBCL. <i>Clin Cancer Res; 22(5); 1138–49. ©2015 AACR</i>.</p></div>