What question did this study set out to answer?

To determine the molecular mechanisms by which the transcription factor EGR1 contributes to acquired ibrutinib resistance in mantle cell lymphoma and diffuse large B-cell lymphoma.

September 22, 2023BloodOpen Access

EGR1-mediated metabolic reprogramming to oxidative phosphorylation contributes to ibrutinib resistance in B-cell lymphoma

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Authors

YLYunxia LiuUniversity of Wisconsin–Madison SKShuichi KimparaUniversity of Wisconsin–Madison NHNguyet M. HoangUniversity of Wisconsin–Madison

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Implication

Preclinical study reveals that EGR1 drives oxidative phosphorylation to induce ibrutinib resistance in B-cell lymphoma, suggesting OXPHOS inhibitors can overcome drug resistance.

Key Points

To determine the molecular mechanisms by which the transcription factor EGR1 contributes to acquired ibrutinib resistance in mantle cell lymphoma and diffuse large B-cell lymphoma.
Assessed EGR1 expression and downstream pathways in ibrutinib-resistant activated B-cell-like DLBCL and MCL cell lines using genetic and pharmacological modulation.
Evaluated the efficacy of targeting oxidative phosphorylation using metformin and IM156 in in vitro assays and patient-derived xenograft (PDX) mouse models.
EGR1 expression was elevated in resistant lymphoma cells through TCF4 regulation and auto-activation, and it increased further following ibrutinib exposure.
EGR1 directly activated PDP1 transcription, driving pyruvate dehydrogenase complex activation and boosting oxidative phosphorylation and ATP production to sustain cell proliferation.
Inhibition of oxidative phosphorylation with metformin or IM156 significantly suppressed the growth of ibrutinib-resistant lymphoma cells both in vitro and in PDX mouse models.

Cite This Study

Liu et al. (2023) studied this question.

synapsesocial.com/papers/6a1892b8d36da06b0a91808f https://doi.org/10.1182/blood.2023020142

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Implication

Preclinical study reveals that EGR1 drives oxidative phosphorylation to induce ibrutinib resistance in B-cell lymphoma, suggesting OXPHOS inhibitors can overcome drug resistance.

EGR1-mediated metabolic reprogramming to oxidative phosphorylation contributes to ibrutinib resistance in B-cell lymphoma

Discussion

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Implication

Key Points

Cite This Study

EGR1-mediated metabolic reprogramming to oxidative phosphorylation contributes to ibrutinib resistance in B-cell lymphoma

Discussion

Member takes

Implication

Key Points

Cite This Study

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