INTRODUCTION: The gamma-chain (gc) is a transducing element shared between several cytokine receptors, that plays a prominent role in immunological functions and cell survival. It is directly involved in the regulation of self-sufficient growth and cell cycle progression in continuous human malignant hematopoietic cell lines, in a concentration dependent manner.
OBJECTIVE: To evaluate the role of gc in the biology of different types of leukemia, through the analysis of gc-expression profile and gc-signaling in different leukemic cells.
METHODS: Leukemic cells were obtained from the bone marrow of 39 newly diagnosed patients with CML, AML, B-pre ALL and T-ALL and healthy controls. Total RNA was extracted and IL2RG, D-type cyclins, BCL-XL and BECLIN-1expression levels were evaluated through Real-Time PCR. The amount of BECLIN-1 protein was evaluated through western blot, using the specific primary antibody.
RESULTS: IL2RG expression was increased, as compared to controls, in ALL cells and, in particular, in B-pre ALL (2.55 fold increase vs 1.57 in T-ALL). A positive correlation between IL2RG and cyclins D2 (R = 0.82) and D3 (R = 0.76) expression levels was found. BCL-XL expression was 57% than controls, while BECLIN-1 expression was 4.73-times higher than controls, suggesting the involvement of autophagy in gc-induced cell survival.
CONCLUSIONS: The gc is prominently over-expressed in B-pre ALL, with a direct correlation with D-type cyclins. The up-regulation of gc also associates with increased BECLIN-1 expression, which is a potent mediator of autophagy
