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.
journal_name
Leuk Lymphomajournal_title
Leukemia & lymphomaauthors
Loi TH,Dai P,Carlin S,Melo JV,Ma DDFdoi
10.3109/10428194.2015.1043545subject
Has Abstractpub_date
2016-02-01 00:00:00pages
411-418issue
2eissn
1042-8194issn
1029-2403journal_volume
57pub_type
杂志文章abstract::Abstract Acute graft-versus-host disease (GVHD) has compromised and continues to compromise the benefits associated with allogeneic hematopoietic cell transplant to cure malignant and non-malignant diseases. Pharmacologic interventions to prevent GVHD have emerged as a major objective of research in the immunology and...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.3109/10428194.2012.762978
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abstract::Thalidomide is thought to have anti-angiogenic and immunomodulatory properties, including suppression of tumor necrosis factor-alpha, effects on interleukins and interferons, down-regulation of some cell adhesion molecules, and changes in the proportion of lymphocyte subsets. It is unclear whether the clinical respons...
journal_title:Leukemia & lymphoma
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doi:10.1080/10428190500078300
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章,多中心研究
doi:10.1080/1042819031000063462
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journal_title:Leukemia & lymphoma
pub_type: 临床试验,杂志文章
doi:10.3109/10428199709109170
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abstract::The number of circulating plasma cells (CPC) was determined on mononuclear cell preparations after Giemsa (morphology) and light chain staining (immunocytochemistry). Both methods gave reproducible and identical results when CPC were 1% or more. Using this limit, no CPC were observed in MGUS (0/11) and primary amyloid...
journal_title:Leukemia & lymphoma
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doi:10.3109/10428199409049709
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abstract::Chronic lymphocytic leukemia (CLL) is at present an incurable disease. All of the drugs used in the treatment of CLL induce apoptosis in the cells, and in vitro responses to glucocorticoid or analogs correlate with in vivo sensitivity to these agents. Since CLL lymphocytes accumulate rather than proliferate, the idea ...
journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
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journal_title:Leukemia & lymphoma
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doi:10.3109/10428199209053627
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章
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journal_title:Leukemia & lymphoma
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journal_title:Leukemia & lymphoma
pub_type: 临床试验,杂志文章
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.3109/10428199109068124
更新日期:1991-01-01 00:00:00
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章,随机对照试验
doi:10.3109/10428194.2015.1106534
更新日期:2016-07-01 00:00:00
abstract::Opportunistic infection with invasive aspergillosis (IA) is increasingly frequent in immunocompromised patients, particularly in those with hematological malignancies. In this setting, IA typically involves the lung, with extra-pulmonary involvement usually occurring in the setting of disseminated infection. We report...
journal_title:Leukemia & lymphoma
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doi:10.1080/10428190400025138
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journal_title:Leukemia & lymphoma
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journal_title:Leukemia & lymphoma
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doi:10.3109/10428190009057629
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章
doi:10.1080/1042819022386716
更新日期:2002-07-01 00:00:00
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章,评审
doi:10.1080/10428190902934944
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journal_title:Leukemia & lymphoma
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doi:10.3109/10428190009148393
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journal_title:Leukemia & lymphoma
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journal_title:Leukemia & lymphoma
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journal_title:Leukemia & lymphoma
pub_type: 临床试验,杂志文章
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journal_title:Leukemia & lymphoma
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doi:10.3109/10428199409051687
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journal_title:Leukemia & lymphoma
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doi:10.1080/10428190500052248
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journal_title:Leukemia & lymphoma
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doi:10.3109/10428194.2013.797088
更新日期:2014-01-01 00:00:00
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journal_title:Leukemia & lymphoma
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doi:10.3109/10428199009053529
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journal_title:Leukemia & lymphoma
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journal_title:Leukemia & lymphoma
pub_type: 临床试验,杂志文章
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journal_title:Leukemia & lymphoma
pub_type: 杂志文章
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journal_title:Leukemia & lymphoma
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