Effects of Adenovirus-mediated Expression of p27-super>Kip1-/super>, p21- super>Waf1-/super> And p16-super>INK4A-/super> in Cell Lines Derived from t(2; 5) Anaplastic Large Cell Lymphoma and Hodgkins Disease

• Published in: Leukemia & lymphoma 2002-01, Vol.43 (6), p.1323-1328
• Main Authors: Turturro, Franceso, Arnold, Marilyn D, Frist, Audrey Y, Seth, Prem
• Format: Article
• Language: English
• ISSN: 1042-8194
• DOI: 10.1080/10428190290021713

We investigated the response of SUDHL-1 and L428 cells, derived from t(2; 5)- anaplastic large cell lymphoma (ALCL) and Hodgkins disease (HD), respectively, to recombinant adenoviruses expressing cyclin-dependent kinase inhibitors (CDKIs) p27-super>Kip1-/super> (Adp27), p21-super>Waf1-/super> (Adp21) and p16- super>INK4A-/super> (Adp16). Cell cycle analysis of SUDHL-1 cells after 24 h of infection with 200 multiplicity of infection (MOI) of Adp27, Adp21, and Adp16, showed very high levels of cell debris in the subG1 area. The magnitude of cell debris-events was -f>Adp27/Adp21>Adp16.-/f> Cell cycle analysis of L428 cells revealed absence of cell debris and increased G2 phase in all the groups of cells tested as compared to the controls (mock and AdNull). A minimal increase in G1 phase was also evident in cells infected with Adp27 (52%) compared to uninfected cells (43%), AdNull (45%) and to cells infected with Adp21 (37%) and Adp16 (31%). The presence of significant levels of Coxsackie-adenovirus receptor (CAR) on the cell surface of L428 cells excluded the cell membrane-barrier as responsible for the differences in cell observed in response to the recombinant adenovirus-mediated CDKIs expression as compared to SUDHL-1. We also showed that the recombinant adenovirus-mediated cytotoxicity measured as apoptosis was MOI- and vector-dependent in SUDHL-1 cells at lower MOI (100). In conclusion, the therapeutic effect induced by recombinant adenoviruses expressing p27-super>Kip1- /super>, p21-super>Waf1-/super> and p16-super>INK4A-/super> is cell-dependent in cells derived from selected lymphoid malignancies. Biochemical cellular differences more than cell surface barriers seem to be responsible for differences in response to recombinant adenovirus-mediated expression of cytotoxic genes. Moreover, the cytotoxicity of recombinant adenoviruses expressing p27-super>Kip1-/super>, p21-super>Waf1-/super> and p16-super>INK4A- /super> may be further explored as a tool for gene therapy of t(2; 5)-derived ALCL.