Pro-survival role of protein kinase C epsilon in Philadelphia chromosome positive acute leukemia. Issue 2 (1st February 2016)

• Record Type: Journal Article
• Authors: Loi, To Ha; Dai, Pei; Carlin, Stephen; Melo, Junia V.; Ma, David D. F.
• Is Part Of: Leukemia & lymphoma. Volume 57:Issue 2(2016:Feb.)
• Page Start: 411
• Page End: 418
• Publication Date: 2016-02-01
• Subjects: BCR-ABL -- imatinib resistance -- PKC epsilon; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2015.1043545
• Languages: English
• ISSNs: 1042-8194

Abstract

Abstract : Durable responses to imatinib monotherapy are rarely seen in aggressive forms of Philadelphia chromosome positive (Ph+) leukemias. To investigate the possible cause of treatment failure we examined the role of protein kinase C epsilon (PKCE), an oncogene highly implicated in the development of solid tumors and resistance to chemotherapy. We found high levels of PKCE transcripts in Ph+ acute lymphoblastic leukemia (ALL) cells from patients and cell lines, and imatinib resistant chronic myeloid leukemia, which were also less responsive to imatinib-induced apoptosis than Ph+ cells with lower PKCE expression. Furthermore, the siRNA-mediated knockdown or peptide inhibition of PKCE in Ph+ cells increased imatinib-induced apoptosis while overexpression of PKCE reduced imatinib-induced apoptosis, with concomitant increase in the pro-survival factor AKT. Our results suggest PKCE plays a protective role against apoptosis induced by BCR-ABL inhibition in Ph+ leukemias with high PKCE expression, such as Ph+ ALL.