The activation of intracellular tyrosine kinases by interferon-alpha (IFN alpha) correlates with its antiproliferative activity in B-lymphoid cell lines, but not in B-cell chronic lymphocytic leukemia patients

The response to interferon-alpha (IFN alpha) treatment in leukemias of the B-cell lineage shows a marked heterogeneity. A distinct subset of patients with B-CLL responds to treatment with IFN alpha, while the drug has no ther apeutic effect in the majority of patients. The mechanism of this phenomeno n is poorly understood. The cellular events induced by this cytokine mediat ed by a number of specific signaling events. Therefore, we studied the effe ct of recombinant IFN alpha on tyrosine phosphorylation and proliferation o f cytosolic proteins in human cell lines and in freshly isolated B-CLL cell s in order to test the potential value of these events as a pretreatment te st for IFN alpha in CLL. In human lymphoid cell lines, IFN alpha induced ty rosine phosphorylation of multiple cytosolic proteins in a time- and concen tration-dependent manner. This effect correlated with its growth-inhibitory effect in almost all cell lines. In marked contrast, in freshly isolated B -CLL cells IFN alpha seemed to have both stimulatory and inhibitory effects on proliferation, but it consistently stimulated tyrosine phosphorylation. Moreover, the clinical response of B-CLL to IFN alpha did not correlate wi th the activation of tyrosine kinases nor with the inhibition of cell growt h in vitro. Therefore, the assessment of IFN alpha-induced tyrosine phospho rylation of cytosolic phosphoproteins does not allow to predict the treatme nt response to IFN alpha in CLL patients.