Publication Date:
2011-11-18
Description:
Abstract 1769 CLL cells are characterized by their ability to resist apoptosis in vivo, but in vitro they undergo spontaneous apoptosis. This suggests that interactions between CLL cells and accessory cells in the tissue microenvironments, such as mesenchymal stromal cells (MSC), nurselike cells (NLC), T-cells, and endothelial cells are critical for maintaining CLL cell survival. CLL cells display constitutive PI3K pathway activation, presumable due to CLL interactions with the microenvironment. CAL-101 is a potent and selective inhibitor of the p110d PI3K isoform and has shown promising clinical activity in chronic lymphocytic leukemia (CLL) in early stage clinical trials. Here, we investigated the ability of CAL-101 to disrupt interactions between CLL and endothelial cells (EC) or bone marrow stromal cells (BMSC). We tested two EC lines human umbilical vein endothelial cells (HUVEC) and UV-2 mouse vascular endothelial cells, and two BMSC lines, stroma-NKtert derived from human bone marrow, and KUSA-H1, a murine BMSC line. CLL cells were cultured for 72h in presence or absence of EC or BMSC. Fig A displays mean (±SEM) CLL cell viabilities of cells from 7 different patients. We found that both, EC and BMSC rescue CLL cells from spontaneous apoptosis with significantly higher CLL cell viabilities in the presence of EC and BMSC (*P〈 0.05; **P〈 0.01). For example, after 48h significantly higher CLL cell viabilities were noticed with HUVEC (53.2%±4.3%, p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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