Expression of sialidase Neu2 in leukemic K562 cells induces apoptosis by impairing Bcr-Abl/Src kinases signaling

Chronic myeloid leukemia is a hematopoietic stem cell cancer,
originated by the perpetually “switched on” activity of the
tyrosine kinase Bcr-Abl, leading to uncontrolled proliferation
and insensitivity to apoptotic stimuli. The genetic phenotype of
myeloid leukemic K562 cells includes the suppression of cytosolic
sialidase Neu2. Neu2 transfection in K562 cells induced a
marked decrease (30% and 80%) of the mRNA of the antiapoptotic
factors Bcl-XL and Bcl-2, respectively, and an almost
total disappearance of Bcl-2 protein. In addition, gene expression and activity of Bcr-Abl underwent a 35% diminution, together with a marked decrease of Bcr-Abl-dependent Src and Lyn kinase activity. Thus, the antiapoptotic axis Bcr-Abl, Src, and Lyn, which stimulates the formation of Bcl-XL and Bcl-2, was remarkably weakened. The ultimate consequences of these modifications were an increased susceptibility to apoptosis of K562 cells and a marked reduction of their proliferation rate. The molecular link between Neu2 activity and Bcr-Abl signaling pathway may rely on the desialylation of some cytosolic glycoproteins.
In fact, three cytosolic glycoproteins, in the range 45–66 kDa, showed a 50–70% decrease of their sialic acid content upon Neu2 expression, supporting their possible role as modulators of the Bcr-Abl complex.