B-cell–specific transcription factor BACH2 modifies the cytotoxic effects of anticancer drugs

Kamio, Takeshi; Toki, Tsutomu; Kanezaki, Rika; Sasaki, Susumu; Tandai, Satoru; Terui, Kiminori; Ikebe, Dai; Igarashi, Kazuhiko; Ito, Etsuro

doi:10.1182/blood-2002-12-3656

Cited by 47 publications

(54 citation statements)

References 34 publications

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“…Relatedly, Kahn et al (114) showed that anticancer conditioning agents (doxorubicin, etoposide, fludarabine phosphate, or vincristine) were able to induce HIV escape from latency and that this was associated with increased apoptosis rates (114). It is interesting to note that these drugs have been reported to induce oxidative stress (115)(116)(117), corroborating previous findings suggesting that the viral reservoir may be redox responsive and could potentially be eliminated by pro-oxidant drugs (118). The case of Mr. Timothy Brown (the "Berlin patient"), who was famously cured of HIV after a hemato- poietic stem cell transplant to treat acute myeloid leukemia, may be instructive.…”

Section: Treating Hiv/aids By Increasing Oxidative Stress: Results Frmentioning

confidence: 99%

Dual targeting of the thioredoxin and glutathione systems in cancer and HIV

Benhar¹,

Shytaj²,

Stamler³

et al. 2016

Journal of Clinical Investigation

149

115

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Section: Treating Hiv/aids By Increasing Oxidative Stress: Results Frmentioning

confidence: 99%

Dual targeting of the thioredoxin and glutathione systems in cancer and HIV

Benhar¹,

Shytaj²,

Stamler³

et al. 2016

Journal of Clinical Investigation

149

115

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“…As mentioned above, ATF4 is also induced by oxidative stress. Unlike ATF4, however, which enables cells to manage stress conditions as part of the protective response (38,48), expression of Bach2 is thought to be associated with suppression of the mechanisms that guard cells against oxidative stress (49).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Signature of Human Cancer Cell Lines Treated with the Ras Inhibitor Salirasib (S-Farnesylthiosalicylic Acid)

Blum¹,

Elkon²,

Yaari³

et al. 2007

Cancer Research

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“…In diffuse large cell lymphoma, where CCND2 overexpression by gene-expression profiling predicts poor prognosis, expression of BACH2 predicts good prognosis (41). Significantly, BACH2 negatively regulates the immunoglobulin 3′ enhancer (27,28,42,43) and may therefore also inhibit expression of oncogenes dysregulated by translocations to this enhancer, including (in MM) CCND1, FGFR3, or MAF.…”

Section: Figurementioning

confidence: 99%

Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity

Tiedemann¹,

Mao²,

Shi³

et al. 2008

J. Clin. Invest.

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Knockout and transgenic studies in mice demonstrate that normal somatic tissues redundantly express 3 cyclin D proteins, whereas tumor cells seem dependent on a single overexpressed cyclin D. Thus, selective suppression of the individual cyclin D deregulated in a tumor represents a biologically valid approach to targeted cancer therapy. In multiple myeloma, overexpression of 1 of the cyclin D proteins is a ubiquitous feature, unifying at least 7 different initiating genetic events. We demonstrate here that RNAi of genes encoding cyclin D1 and cyclin D2 (CCND1 and CCND2, respectively) inhibits proliferation and is progressively cytotoxic in human myeloma cells. By screening a chemical library using a cell-based assay for inhibition of CCND2 trans-activation, we identified the plant cytokinin kinetin riboside as an inhibitor of CCND2 trans-activation. Kinetin riboside induced marked suppression of CCND2 transcription and rapidly suppressed cyclin D1 and D2 protein expression in primary myeloma cells and tumor lines, causing cell-cycle arrest, tumor cell-selective apoptosis, and inhibition of myeloma growth in xenografted mice. Mechanistically, kinetin riboside upregulated expression of transcription repressor isoforms of cAMP-response element modulator (CREM) and blocked both trans-activation of CCND2 by various myeloma oncogenes and cis-activation of translocated CCND1, suggesting induction of an overriding repressor activity that blocks multiple oncogenic pathways targeting cyclin D genes. These data support targeted repression of cyclin D genes as a therapeutic strategy for human malignancies. IntroductionMultiple myeloma (MM) is a postgerminal center B cell malignancy characterized by clonal plasma cell expansion. The disease manifests clinically with anemia, monoclonal immunoglobulin, renal insufficiency, and lytic bone lesions and currently affects 63,000 people in the United States alone (1); moreover, as it is currently incurable, MM causes a disproportionate 2% of all cancer deaths.Although myeloma tumors present with complex karyotypes and an assortment of structural and numerical chromosomal abnormalities, these tumors are unified in their ubiquitous targeting of cyclin D genes for overexpression. Of MM tumors, 54% overexpress cyclin D1 (CCND1), 48% overexpress cyclin D2 (CCND2), 3% overexpress cyclin D3 (CCND3), and 8% overexpress both CCND1 and CCND2 (2). Deregulated expression of single CCND genes in MM occurs as the result of selective cyclin D gene trans-activation by deregulated transcription factors or from translocation of a single

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B-cell–specific transcription factor BACH2 modifies the cytotoxic effects of anticancer drugs

Cited by 47 publications

References 34 publications

Dual targeting of the thioredoxin and glutathione systems in cancer and HIV

Dual targeting of the thioredoxin and glutathione systems in cancer and HIV

Gene Expression Signature of Human Cancer Cell Lines Treated with the Ras Inhibitor Salirasib (S-Farnesylthiosalicylic Acid)

Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity

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