Author/Authors :
EI-Tounsi, Iman Menoufeya Faculty of Medicine - Department of Clinical Pathology, Egypt , Alenzi, Faris Q. B. King Faisal University - College of Applied Biomedical Sciences - Department of Clinical Laboratory Sciences, Section of Immunology, Saudi Arabi
Abstract :
Survivin, a member of the inhibitors of apoptosis gene family, is expressed in a cell-cycle-dependent manner in most common cancers but not in normal differentiated adult tissues. Survivin is expressed in acute myeloid leukemia (AML). Survivin is also detected in all myeloid leukemia cell lines. In contrast, normal CD34+ cells and normal peripheral blood mononuclear cells express no or very low levels of survivin. Cytokine stimulation increased survivin expression in leukemic cell lines and in primary AML samples. TRAIL is a member of the TNF superfamily of ligands. TRAIL is known to induce apoptosis through the extrinsic pathway. The latter implies the activation of a cascade of caspases. We examined the modulation of survivin expression, following addition of TRAIL, in 12 primary AML samples, 7 normal CD34+ samples, as well as in 3 myeloid cell lines (HL-60, HL-60 Dox and OCI-AML3). In culture of primary samples, single-TRAIL treatment increased survivin expression in TRAIL resistant AML as well as in normal CD34+ samples, in comparison with control cells. TRAIL also increased survivin expression in HL-60 and OCI-AML3 but not in HL-60 Dox cell line which is transfected with Doxorubicin drug resistance gene, suggesting no possible role of drug resistance in stimulating survivin expression following treatment with TRAIL. In conclusion, these results demonstrate that survivin is highly expressed and TRAIL-modulated in myeloid leukemias and suggest that one of the alternate resistance mechanisms to TRAIL induction of apoptosis in AML may be due to, at least in part, by increasing survivin levels.
