Abstract 702: Drug resistance and invasion in diffuse large B-cell lymphoma are mediated by Akt, 14-3-3ζ, and Vimentin

Author(s):  
Evan M. Cherry ◽  
Kayla J. Bayless ◽  
Steve A. Maxwell
Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5316-5316
Author(s):  
Qinjun Zhou ◽  
Yongqiang Wei ◽  
Xiaolei Wei ◽  
Qi Wei ◽  
Ru Feng

Abstract CD44, a transmembrane glycocoptotein, involved in tumor cell survival, migration , invasion, metastasis and prognosis of many cancers. This study was performed to investigate the effects of CD44 over expression on the biological function and the chemotherapeutic sensitivity of ABC-DLBCL. The full length CD44 cDNA was cloned into pEASY-T vector and then transfected into activated B cell-like diffuse large B-cell lymphoma cell line OCI-ly3. QPCR and western blot confirmed that the CD44 expression was up-regulated in both mRNA and protein levels in CD44-transfected OCI-ly3 cells. The cell proliferation of OCI-ly3-CD44 cells was significantly faster than that in OCI-ly3-GFP cells and the OCI-ly3 cells (p<0.001). Annexin V-APC/PI staining results showed that the apoptosis ratio wasn't difference among three groups (p=0.676). OCI-ly3-CD44 cells showed significantly higher migration ratio than OCI-ly3-GFP cells and the OCI-ly3 cells(p=0.031). The IC50 of doxorubicin in OCI-ly3-CD44 cells (0.348±0.072uM) was higher than that in OCI-ly3-GFP (0.348±0.072uM ) and OCI-ly3cells(0.138±0.029uM ) ( P<0.001). After treatment with doxorubicin for 24h, the OCI-ly3-CD44 cells showed lower apoptotic ratio than OCI-ly3-GFP and OCI-ly3 cells ( (17.5±1.33)% VS. (41.7±9.91) %, (41.8±7.23)%), P<0.001). In conclusion, CD44 plays a key role in cell growth regulation and chemo-resistance and is a potential target to overcome drug resistance and improve prognosis in DLBCL. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Author(s):  
Xuzhao Zhang ◽  
Zhaoxing Wu ◽  
Yun Liang ◽  
Jinfan Li ◽  
Liansheng Huang ◽  
...  

Abstract BackgroundAlthough treatment of diffuse large B-cell lymphoma (DLBCL) has progressed considerably in recent years, treatment failure still occurs in about 40% of patients who are refractory/relapse. Recent studies suggest that TP53 mutation may be an important cause of refractory/relapse in DLBCL, but the cause of TP53 mutation remains unclear. MethodsIn the present study, the correlation between TP53 mutation status and APOBEC3A and APOBEC3B expression in DLBCL specimens was searched by detecting the correlation between TP53 mutation and APOBEC3B expression in combination with database informatics analysis. Further, the relationship between APOBEC3B expression and TP53 mutation was analyzed by constructing APOBEC3B induced expression DLBCL cell lines. The effects of APOBEC3B-induced TP53 mutants on DLBCL cell proliferation and drug resistance were also tested. ResultsWe identify APOBEC3B as a critical factor that regulates p53-mutant driven drug resistance of DLBCL. APOBEC3B induces TP53 mutations of DLBCL cells, and its mutation patterns are similar to those in DLBCL patients. Moreover, APOBEC3B-induced p53 mutants promoted growth of DLBCL cells as well as contributed to drug resistance. In human DLBCL, APOBEC3B is aberrantly activated and associated with p53 mutant-mediated refractory/relapsed DLBCL. ConclusionThese findings yield insights into the mechanism of refractory/relapsed DLBCL induced by p53 mutants and reveal APOBEC3B as a new therapeutic target.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Luc-Matthieu Fornecker ◽  
Leslie Muller ◽  
Frédéric Bertrand ◽  
Nicodème Paul ◽  
Angélique Pichot ◽  
...  

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