Death receptor 4 is preferentially recruited to lipid rafts in CLL cells contributing to tumor necrosis related apoptosis inducing ligand-induced synergistic apoptotic responses.

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BlankDeath receptor 4 is preferentially recruited to lipid rafts in chronic

lymphocytic leukemia cells contributing to tumor necrosis related apoptosis

inducing ligand-induced synergistic apoptotic responses.

W Xiao, G Ishdorj, J Sun, JB ston, and SB Gibson

Leuk Lymphoma, July 1, 2011; 52(7): 1290-301.

Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, MB,

Canada.

Tumor necrosis related apoptosis inducing ligand receptor 1 (TRAIL-R1, death

receptor 4 [DR4]) and TRAIL-R2 (DR5) have been proposed as targets for cancer

therapy, but which death receptor to target for chemotherapy in chronic

lymphocytic leukemia (CLL) is uncertain. Herein, we discovered that Burkitt

lymphoma B cell line, BJAB, CLL-like cell line, I-83, and pre-acute lymphocytic

leukemia B cell line, NALM-6, underwent apoptosis following TRAIL, whereas a

CLL-like cell line, JMV-3, and primary CLL cells failed to undergo apoptosis. In

TRAIL resistant CLL cells, only activation of DR4 provided an increase in

fludarabine induced apoptosis. This was mediated in part by the localization of

DR4 but not DR5 in lipid rafts following TRAIL and fludarabine treatment. This

preference for DR4 activation leading to increased fludarabine induced apoptosis

was also observed following SAHA, PS-341, and chlorambucil treatment in primary

CLL cells. Thus, CLL cells selectively activate DR4 partially mediated through

its localization to lipid rafts leading to apoptosis when combined with

chemotherapeutic drugs.

PMID: 21699383