Guilty bystanders: nurse-like cells as a model of microenvironmental support for leukemic lymphocytes

• DOI: 10.1007/s10238-013-0268-z
• Publication Date: 2013-12-11T10:21:33Z
• Authors: Agata A. Filip; Bogumiła Ciseł; Ewa Wąsik-Szczepanek
• Keywords: Survivin; XIAP; Ex vivo; Viability assay; Hematology

B-cell chronic lymphocytic leukemia (B-CLL) is one of the most common leukemias among elderly and, despite many efforts, still stays incurable. Recent studies point to microenvironment as critical factor providing leukemic lymphocytes with pro-survival signals. Thus, neighboring cells appear be a perfect target for antileukemic therapy. Nurse-like (NLCs) largely contribute CLL microenvironmental support. We developed lymphocyte/NLC co-culture model investigation interactions. Viability and apoptosis were investigated in treated dexamethasone (DEX) chlorambucil (CLB), without NLCs' For first time, capacity DEX CLB affect NLCs viability was also evaluated. Apoptosis-associated gene expression profiles ex vivo cultured assessed by arrays. escaped spontaneous several months when NLCs. The presence significantly reduced induced (p < 0.001; p = 0.012, respectively), their protective effect more evident than recombinant SDF1. Both decreased viability, but lesser extent (mean DEX-treated cultures 37.79% compared 29.24% lymphocytes). important anti-apoptotic genes lymphocytes; median BCL2, SURVIVIN, BCL2A1, XIAP higher status. makes up convenient close natural-state studying relationship between microenvironment. Direct cell-to-cell contact increases lymphocytes, thus protecting them against apoptosis. As drugs not so apparent NLCs, combined therapy targeted at both should considered patients. Simultaneous aiming disruption different signaling pathways and/or proteins may further improve treatment efficiency.