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Volume 8, Issue 2 (Suppl) J Blood Disord Transfus
ISSN: 2155-9864 JBDT, an open access journal Hematologists 2017
May 08-09, 2017
7th World Hematologists Congress
May 08-09, 2017 Barcelona, Spain
PTEN status and Akt phosphorylation: Implications for the rituximab-resistance in B-cell lymphoma
Jingjing Wu
First Affiliated Hospital of Zhengzhou University, China
Rituximab has been widely used in clinical practice for the treatment of B-cell malignancies, but the majority of patients retreated
with rituximab will eventually relapse with variable degrees of resistant disease. There is an urgent need to explore the mechanisms
of resistance to rituximab in non–Hodgkin’s lymphoma (NHL), and to develop therapeutic strategies to overcome resistance. Herein,
we successfully set up three types of rituximab-resistant B lymphoma cell lines with different malignancy grade, and demonstrate
that phosphatase and tensin homolog (PTEN) is low expressed in the rituximab-resistant cell lines. Furthermore, we report that
reduced PTEN expression correlated with resistance to rituximab and inhibited tumor cell apoptosis through activation of Akt
phosphorylation. Restoration of PTEN expression resulted in re-sensitization of resistant cells to rituximab through modulation
of apoptosis by suppressing the p-Akt in the PI3K/Akt signaling pathway. Overall, our findings demonstrate a novel mechanism
of rituximab-resistance by the involvement of PTEN status and Akt phosphorylation in three different types of rituximab-resistant
B lymphoma cell lines, which may be new predictive markers for response to rituximab and provide new insights for reversing
rituximab resistance in B-cell lymphoma.
Understanding the epigenetic response in resistant cancer cells to romidepsin therapy
Ellen McAuley
University of Liverpool, UK
The histone deacetylase inhibitor (HDACi) romidepsin has shown therapeutic potential in the treatment of peripheral and
cutaneous T cell lymphoma although resistance to this novel therapeutic agent often develops. Multiple mechanisms of resistance
to HDACis have been identified in vitro, but how this class of epigenetic inhibitors manipulates the epigenome and whether this
is altered to cause development of tolerance in cancer cells has not been studied. Previous work in the department into HDACi
resistance has identified candidate epigenetic genes, including HDAC8 and KDM5A, whose mRNA expression pattern is perturbed
in response to HDACi treatment in multiple romidepsin resistant cell lines. However, whether these alterations in mRNA levels
reflect protein expression and functional changes remains unclear. Using the CTCL cell line HuT78 and its romidepsin resistant
counterpart (RHuT78), it was shown that both HDAC8 and the KDM5A protein expression are altered differently between the wild
type and the resistant cell line upon treatment with romidepsin. Furthermore, by combining romidepsin treatment with the DNA
methyltransferase inhibitor 5-azacytidine and inducing an apoptotic response in RHuT78 cells, the expression changes of HDAC8
and KDM5A could be transformed back to that seen in the parental HuT78 cell line. These results suggest that both HDAC8 and
KDM5A may contribute towards defining resistant responses to HDACis and are therefore worthy for further study into potential
therapeutic targets for inhibition to overcome resistance to romidepsin.
J Blood Disord Transfus 2017, 8:2(Suppl)