Pro-survival role of protein kinase C epsilon in Philadelphia chromosome positive acute leukemia
Date
2016
Authors
Loi, T.
Dai, P.
Carlin, S.
Melo, J.
Ma, D.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Leukemia and Lymphoma, 2016; 57(2):411-418
Statement of Responsibility
To Ha Loi, Pei Dai, Stephen Carlin, Junia V. Melo and David D. F. Ma
Conference Name
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.
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
© 2015 Informa UK, Ltd.