Pro-survival role of protein kinase C epsilon in Philadelphia chromosome positive acute leukemia

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...

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Bibliographic Details
Published inLeukemia & lymphoma Vol. 57; no. 2; pp. 411 - 418
Main Authors Loi, To Ha, Dai, Pei, Carlin, Stephen, Melo, Junia V., Ma, David D. F.
Format Journal Article
LanguageEnglish
Published United States Taylor & Francis 01.02.2016
Subjects
BCR-ABL
imatinib resistance
PKC epsilon
imatinib resistance
PKC epsilon
BCR-ABL
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Summary: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.
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ISSN:1042-8194
1029-2403
DOI:10.3109/10428194.2015.1043545