What question did this study set out to answer?

To identify molecular drivers of kinase-independent tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia (CML).

March 12, 2021OncogeneOpen Access

Proteasome 26S subunit, non-ATPases 1 (PSMD1) and 3 (PSMD3), play an oncogenic role in chronic myeloid leukemia by stabilizing nuclear factor-kappa B

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Authors

ABAlfonso E. Bencomo‐Alvarez ARAndres J. Rubio IOIdaly M. Olivas

Discussion

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Overview

Preclinical study demonstrates that PSMD1 and PSMD3 promote kinase-independent drug resistance in chronic myeloid leukemia via NF-κB stabilization, highlighting potential therapeutic targets.

Key Points

To identify molecular drivers of kinase-independent tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia (CML).
Performed genome-wide expression profiling, nucleocytoplasmic fractionation, and luciferase reporter assays in TKI-resistant versus sensitive CML cell lines and CD34+ patient cells.
Evaluated PSMD1 and PSMD3 expression across chronic and blast phases of CML and knocked down both genes in CML cells and normal cord blood CD34+ progenitor cells.
TKI-resistant CML cells demonstrated heightened nuclear NF-κB activity and marked upregulation of proteasome subunits PSMD1 and PSMD3, with highest transcript levels found in blast phase patients.
Knockdown of PSMD1 or PSMD3 impaired survival and triggered apoptosis selectively in CML cells while sparing healthy cord blood progenitors, mediated by downregulation of NF-κB and downstream STAT3 signaling.

Cite This Study

Bencomo‐Alvarez et al. (2021) studied this question.

synapsesocial.com/papers/6a751cbaf2cd31a1fadbf8c1 https://doi.org/10.1038/s41388-021-01732-6

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March 12, 2021OncogeneOpen Access

Proteasome 26S subunit, non-ATPases 1 (PSMD1) and 3 (PSMD3), play an oncogenic role in chronic myeloid leukemia by stabilizing nuclear factor-kappa B

View Full Paper

Ask AI

Bookmark

Authors

ABAlfonso E. Bencomo‐Alvarez ARAndres J. Rubio IOIdaly M. Olivas

Discussion

Member takes

Overview

Preclinical study demonstrates that PSMD1 and PSMD3 promote kinase-independent drug resistance in chronic myeloid leukemia via NF-κB stabilization, highlighting potential therapeutic targets.

Key Points

To identify molecular drivers of kinase-independent tyrosine kinase inhibitor (TKI) resistance in chronic myeloid leukemia (CML).
Performed genome-wide expression profiling, nucleocytoplasmic fractionation, and luciferase reporter assays in TKI-resistant versus sensitive CML cell lines and CD34+ patient cells.
Evaluated PSMD1 and PSMD3 expression across chronic and blast phases of CML and knocked down both genes in CML cells and normal cord blood CD34+ progenitor cells.
TKI-resistant CML cells demonstrated heightened nuclear NF-κB activity and marked upregulation of proteasome subunits PSMD1 and PSMD3, with highest transcript levels found in blast phase patients.
Knockdown of PSMD1 or PSMD3 impaired survival and triggered apoptosis selectively in CML cells while sparing healthy cord blood progenitors, mediated by downregulation of NF-κB and downstream STAT3 signaling.

Cite This Study

Bencomo‐Alvarez et al. (2021) studied this question.

synapsesocial.com/papers/6a751cbaf2cd31a1fadbf8c1 https://doi.org/10.1038/s41388-021-01732-6

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