What question did this study set out to answer?

To identify the regulatory mechanisms causing constitutive Nrf2 activation in acute myeloid leukemia and determine its contribution to chemotherapy resistance.

October 18, 2012BloodOpen Access

The high Nrf2 expression in human acute myeloid leukemia is driven by NF-κB and underlies its chemo-resistance

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Authors

SRStuart A. RushworthUniversity of East Anglia LZLyubov ZaitsevaUniversity of East Anglia MMMegan Y. MurrayUniversity of East Anglia

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Implication

Laboratory study reveals NF-κB-driven Nrf2 overexpression promotes chemoresistance in acute myeloid leukemia cells, indicating targeting this pathway may improve chemotherapy response.

Key Points

To identify the regulatory mechanisms causing constitutive Nrf2 activation in acute myeloid leukemia and determine its contribution to chemotherapy resistance.
Compared constitutive Nrf2 and Keap1 mRNA and protein expression in human acute myeloid leukemia cells against normal CD34(+) control cells.
Investigated transcriptional regulation using promoter assays, chromatin immunoprecipitation, NF-κB inhibitors, and siRNA targeting NF-κB subunits p50 and p65.
Evaluated leukemia cell clonogenicity and sensitivity to cytotoxic chemotherapy following lentiviral miRNA-mediated knockdown of Nrf2 in patient-derived cells.
Acute myeloid leukemia cells displayed elevated constitutive nuclear Nrf2 driven by an imbalance in Nrf2 and Keap1 mRNA levels rather than somatic mutations.
NF-κB subunits p50 and p65 directly promoted Nrf2 transcription via a specific promoter κB-site, which was reversible with NF-κB inhibitors.
Lentiviral knockdown of Nrf2 significantly suppressed the clonogenicity of primary leukemia cells and restored responsiveness to chemotherapeutic agents.

Cite This Study

Rushworth et al. (2012) studied this question.

synapsesocial.com/papers/6a6fd1c2e5469ee92be0a640 https://doi.org/10.1182/blood-2012-04-422121

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Implication

Laboratory study reveals NF-κB-driven Nrf2 overexpression promotes chemoresistance in acute myeloid leukemia cells, indicating targeting this pathway may improve chemotherapy response.

The high Nrf2 expression in human acute myeloid leukemia is driven by NF-κB and underlies its chemo-resistance

Discussion

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Implication

Key Points

Cite This Study

The high Nrf2 expression in human acute myeloid leukemia is driven by NF-κB and underlies its chemo-resistance

Discussion

Member takes

Implication

Key Points

Cite This Study

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