AIDS-related Non Hodgkin Lymphoma (AIDS-NHL) constitutes an aggressive variety of lymphomas characterized by their increased extranodal involvement, relapse rate and resistance to chemotherapy. In the present era of target-specific therapy, PKC\#946; targeting showed promising results in preclinical studies, as well as phase II clinical trials involving a wide variety of cancers. Studies describing the role of PKC\#946; in AIDS-NHL are primitive if not lacking, and HIV infection was always considered an exclusion criterion in clinical studies involving PKC\#946; inhibition in NHL patients. In our study, we describe the effect of PKC\#946; inhibition on a variety of AIDS-NHL. Three cell lines were studied: The 2F7 (AIDS-Burkitt's Lymphoma), BCBL-1 (AIDS-Primary Effusion Lymphoma) and UMCL01-101 (AIDS-Diffuse Large B Cell Lymphoma). Cells were tested for PKC\#946;1 and PKC\#946;2 expression by immunoblot. Cell viability was measured in the presence of a PKC\#946; specific inhibitor at concentrations of 5, 10, 20 and 30 µM for 48 hours in the presence of 10% fetal bovine serum (FBS). MTS assay was performed to quantify cell viability. Results showed that 2F7 and UMCL01-101 cell lines express PKC\#946;1 and PKC\#946;2, while BCBL-1 expresses only PKC\#946;1 and lacks PKC\#946;2 expression. 2F7 and BCBL-1 were sensitive to PKC\#946; inhibitor. 2F7 showed a maximum of 84% inhibition at 30 µM of inhibitor. BCBL-1 was more sensitive showing a maximum of 91.8% inhibition at 30 µM of inhibitor. The latter finding was unexpected in the absence of PKB\#946;2 expression and implicates PKC\#946;1 as a regulator in these cells. UMCL01-101 bypassed PKC\#946; inhibition and continue to proliferate at low concentrations (5 and 10 µM). These results indicate that PKC\#946; plays an important role in AIDS-related NHL survival, and suggest that PKC\#946; targeting should be considered in a broader spectrum of NHL. Ongoing studies will detail the mechanism of PKC\#946; inhibition and uncover the underlying mechanism of resistance in PKC\#946; expressing UMCL01-101 cells. This mechanism may be considered for exclusion from treatment.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3645.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO