Lack of BCL-2 confers interferon-alpha sensitivity to B-cell lymphomas

Abstract

Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder with pathological manifestations usually including splenomegaly and panctopenia. Interferons (IFNs), specifically of the α subtypes have shown a significant anti-tumor effect in HCL patients, with improvement of hematological parameters within the first few months of treatment. However, the therapeutic effect of IFN-α is still rather limited. The mechanisms responsible for the beneficial action of IFN-α in HCL patients are unclear. A continuous line of cells (Eskol) from a patient diagnosed with HCL was established and shown to have several properties of HCL. Even though, Eskol cells are very resistant to anti-proliferative activity of IFN-α, Daudi cells, another human B-cell-derived cell line, are very sensitive to anti-proliferative activity of IFN-α and are commonly used as a model cell to test anti-proliferative effect of IFN-α. To understand the molecular reason(s) behind the observed obvious differences to IFN sensitivity of above cells, we have analyzed the expression levels of BCL2, caspase-1, Laminin and PARP in these cells. We found that Daudi cells do not express BCL2 at all, and probably because of that, these cells have constantly cleaved, and probably activated form of caspase-1. However, when we overexpresed BCL2 in these cells, they lost processed form of caspase-1 and became resistant to anti-proliferative activity of IFN-α. These results let us to suggest that IFN-α sensitivity of B-cell lymphomas, once again, depends on the presence or absence of BCL2.