Glycodendrimer PPI as a Potential Drug in Chronic Lymphocytic Leukaemia. The Influence of Glycodendrimer on Apoptosis in In Vitro B-CLL Cells Defined by Microarrays
Background: Chronic lymphocytic leukaemia (CLL) cells are characterized by failures in the apoptosis
pathway and increased proliferation, resulting in the progressive accumulation of B-lymphocytes in blood. Despite the
wide range of antileukaemic drugs, CLL remains an incurable disease. However, a breakthrough is expected which
will allow more effective treatment.
Objective: The study investigates the influence of poly(propyleneimine) (PPI) dendrimer with peripheral amino
groups, 30% of which were coated with maltotriose (PPI-G4-OS-Mal-III), on CLL cells, and demonstrates that it acts
through the induction of the apoptotic mechanism. It is important to note that the dendrimer was used as a drug itself
and not as a drug carrier.
Method: CLL and normal lymphocytes were treated in vitro with the dendrimer, either alone or in combination with
fludarabine (FA). The percentages of apoptotic and necrotic cells, and the protein expression, were checked using a
flow cytometer. Gene expression was screened using a two-colour microarray with 60-mer probes.
Results: The results confirm that PPI-G4-OS-Mal-III influences the viability of CLL cells in vitro and does not exert
any significant harmful effect on normal lymphocytes. The dendrimer appears to significantly influence gene and
protein expression in CLL cells.
Conclusion: Since dendrimers can be specifically targeted, they may be very effective in CLL therapy, especially since
in vitro PPI-G4-OS-Mal-III has been found to have stronger effect than fludarabine.
Keywords: Apoptosis, chronic lymphocytic leukaemia (CLL), dendrimers, gene expression, glycodendrimers, poly(propylene imine) (PPI),
protein expression, toxicity.
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