Expression of interferon consensus sequence binding protein induces potent immunity against BCR/ABL-induced leukemia

Deng, Ming; Daley, George Q.

doi:10.1182/blood.v97.11.3491

Cited by 46 publications

(39 citation statements)

References 44 publications

(47 reference statements)

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“…However, IRF8 appears to exert its anti-leukemic activity also by modulating immunity. The coexpression of IRF8 in a BCR-ABL-transformed mouse pro-B cell line induces a CD8 + cytotoxic T cell response that prevents the in vivo establishment of leukemia in a CCL6-and CCL9-dependent manner [70,71]. Indeed, it has long been suggested that CML is highly sensitive to T cell-mediated tumor immunity.…”

Section: As Already Mentioned Irf8mentioning

confidence: 99%

Regulation of myelopoiesis by the transcription factor IRF8

2015

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Section: As Already Mentioned Irf8mentioning

confidence: 99%

Regulation of myelopoiesis by the transcription factor IRF8

2015

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“…The methods to establish these cell lines and their culture conditions were described previously. [24][25][26] Primary CML cells were isolated from fresh peripheral blood samples from CML patients after obtaining informed consent in accordance with a research protocol approved by MD Anderson Cancer Center institutional review board (IRB). Cells were isolated using gradient centrifugation with Fico/Lite lymphoH (d ¼ 1.077, Atlanta Biologicals, Atlanta, GA, USA).…”

Section: Cell Culture and Isolation Of Primary CML Cellsmentioning

confidence: 99%

Effective killing of Gleevec-resistant CML cells with T315I mutation by a natural compound PEITC through redox-mediated mechanism

Zhang

Trachootham

et al. 2008

Leukemia

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Mutation of Bcr-Abl is an important mechanism by which chronic myelogenous leukemia (CML) cells become resistant to Gleevec. The T315I mutation is clinically significant since CML cells harboring this mutation are insensitive to Gleevec and other Bcr-Abl-targeted drugs. Identification of new agents capable of effectively killing CML cells with T315I mutation would have important therapeutic implications in Gleevecresistant CML. Here, we showed that b-phenylethyl isothiocyanate (PEITC), a natural compound found in vegetables, is effective in killing CML cells expressing T315I BCR-ABL. Treatment of leukemia cell lines harboring wild-type or mutant Bcr-Abl with 10 lM PEITC resulted in an elevated ROS stress and a redox-mediated degradation of the BCR-ABL protein, leading to massive death of the leukemia cells. Antioxidant NAC attenuated the PEITC-induced oxidative stress in CML cells and prevented the degradation of BCR-ABL, caspase-3 activation and cell death. We further showed that the ROS-induced degradation of BCR-ABL was mediated partially by caspase-3 and the proteasome pathway. The ability of PEITC to effectively kill T315I-positive CML cells was further confirmed using primary leukemia cells isolated from CML patients. Our results suggest that PEITC is a promising compound capable of killing Gleevec-resistant CML cells through a ROS-mediated mechanism and warrants further investigations.

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“…Mice with IRF-8 null mutation are defective in the ability of myeloid progenitor cells to mature toward macrophage lineage and eventually develop chronic myelogenous leukemia (CML)-like syndrome (6,12). Furthermore, IRF-8 blocks the development of murine Bcr-Ablinduced CML (13) through the inhibition of Bcl-2 (14) and induction of anti-leukemic immunity (15). In humans, down-regulation of IRF-8 expression was reported in CML and acute myelocytic leukemia (AML) patients.…”

mentioning

confidence: 99%

Interferon Regulatory Factor-8 Is Indispensable for the Expression of Promyelocytic Leukemia and the Formation of Nuclear Bodies in Myeloid Cells

Dror

Rave-Harel

Burchert

et al. 2007

Journal of Biological Chemistry

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Interferon (IFN) regulatory factor-8 (IRF-8), previously known as ICSBP, is a myeloid cell essential transcription factor. Mice with null mutation in IRF-8 are defective in the ability of myeloid progenitor cells to mature toward macrophage lineage. Accordingly, these mice develop chronic myelogenous leukemia (CML). We demonstrate here that IRF-8 is an obligatory regulator of the promyelocytic leukemia (PML) gene in activated macrophages, leading to the expression of the PML-I isoform. This regulation is most effective together with two other transcription factors, IRF-1 and PU.1. PML is a tumor suppressor gene that serves as a scaffold protein for nuclear bodies. IRF-8 is not only essential for the IFN-␥-induced expression of PML in activated macrophages but also for the formation of nuclear bodies. Reduced IRF-8 transcript levels were reported in CML patients, and a recovery to normal levels was observed in patients in remission following treatment with IFN-␣. We demonstrate a significant correlation between the levels of IRF-8 and PML in these CML patients. Together, our results indicate that some of the myeloleukemia suppressor activities of IRF-8 are mediated through the regulation of PML. When IRF-8 levels are compromised, the reduced PML expression may lead to genome instability and eventually to the leukemic phenotype.

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Expression of interferon consensus sequence binding protein induces potent immunity against BCR/ABL-induced leukemia

Cited by 46 publications

References 44 publications

Regulation of myelopoiesis by the transcription factor IRF8

Regulation of myelopoiesis by the transcription factor IRF8

Effective killing of Gleevec-resistant CML cells with T315I mutation by a natural compound PEITC through redox-mediated mechanism

Interferon Regulatory Factor-8 Is Indispensable for the Expression of Promyelocytic Leukemia and the Formation of Nuclear Bodies in Myeloid Cells

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