Induction of apoptosis by proteasome inhibitors in B-CLL cells is associated with downregulation of CD23 and inactivation of Notch2

Duechler, Markus; Shehata, Medhat; Schwarzmeier, Josef D.; Hoelbl, Andrea; Hilgarth, Martin; Hubmann, Rainer

doi:10.1038/sj.leu.2403592

Cited by 63 publications

(55 citation statements)

References 47 publications

(59 reference statements)

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“…In support of this view, Duechler et al (2005) reported that bortezomib decreased the surface expression of CD23 in chronic lymphocytic leukemia. Therefore, we investigated the effect of bortezomib and other anti-myeloma drugs on the expression of adhesion molecules on MM cell lines.…”

Section: Downregulation Of Cd49d Expression By Bortezomibsupporting

confidence: 51%

Bortezomib overcomes cell adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma

et al. 2008

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Section: Downregulation Of Cd49d Expression By Bortezomibsupporting

confidence: 51%

Bortezomib overcomes cell adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma

et al. 2008

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“…FZD2 (frizzled homologue 2) is part of the Wnt pathway that includes the TCF7L1 gene that encodes the TCF-3 transcription factor, indicating that Wnt signaling may play a role in resistance. NOTCH2 is overexpressed in B-cell chronic lymphocytic leukemia and might also contribute to the inhibition of apoptosis in B-cell chronic lymphocytic leukemia (35), and constitutively active NOTCH2 decreases protease inhibitor-induced apoptosis in a human B-cell line (36).…”

Section: Discussionmentioning

confidence: 99%

Identification of Expression Signatures Predictive of Sensitivity to the Bcl-2 Family Member Inhibitor ABT-263 in Small Cell Lung Carcinoma and Leukemia/Lymphoma Cell Lines

Tahir

Wass

Joseph

et al. 2010

Molecular Cancer Therapeutics

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ABT-263 inhibits the antiapoptotic proteins Bcl-2, Bcl-x L , and Bcl-w and has single-agent efficacy in numerous small cell lung carcinoma (SCLC) and leukemia/lymphoma cell lines in vitro and in vivo. It is currently in clinical trials for treating patients with SCLC and various leukemia/lymphomas. Identification of predictive markers for response will benefit the clinical development of ABT-263. We identified the expression of Bcl-2 family genes that correlated best with sensitivity to ABT-263 in a panel of 36 SCLC and 31 leukemia/ lymphoma cell lines. In cells sensitive to ABT-

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“…52 Although no Notch mutations have been reported in CLL, emerging data suggest an antiapoptotic role for aberrant Notch activity in this malignancy as well. 53,54 Unlike normal B cells, CLL cells express both Notch 1 and 2, and their ligands Jagged 1 and 2. Coexpression of the Notch receptors and their ligands results in constitutive Notch signaling.…”

Section: Transcriptional Targets Of P53mentioning

confidence: 99%

p53 and Notch signaling in chronic lymphocytic leukemia: clues to identifying novel therapeutic strategies

2011

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The p53 tumor suppressor protein has a key role in the induction of apoptosis of chronic lymphocytic leukemia (CLL) cells. Abnormalities within the p53 pathway identify a subset of patients with a poor prognosis. This review describes recent advances in understanding the mechanisms that regulate p53 levels and the role of p53 in the control of the cell cycle and of apoptosis. The classical model of p53-mediated apoptosis emphasizes the transcriptional activation of proapoptotic genes. In contrast, a novel model emphasizes p53's non-transcriptional actions as the major route of apoptosis induction, whereas its transcriptional arm predominantly upregulates antiapoptotic genes, thus providing a negative feedback mechanism that limits apoptosis. Further studies have identified the Notch pathway as a candidate p53-induced antiapoptotic mechanism. In contrast to the classical model, the novel model predicts that pharmacological inhibition of p53's transcriptional function or of the Notch signaling pathway will augment apoptosis induction by cytotoxic agents. Therapeutic strategies based on the novel model, which we review here for the first time, may significantly augment the antitumor actions of cytotoxic agents in CLL and in other malignancies.

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Induction of apoptosis by proteasome inhibitors in B-CLL cells is associated with downregulation of CD23 and inactivation of Notch2

Cited by 63 publications

References 47 publications

Bortezomib overcomes cell adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma

Bortezomib overcomes cell adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma

Identification of Expression Signatures Predictive of Sensitivity to the Bcl-2 Family Member Inhibitor ABT-263 in Small Cell Lung Carcinoma and Leukemia/Lymphoma Cell Lines

p53 and Notch signaling in chronic lymphocytic leukemia: clues to identifying novel therapeutic strategies

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