New ProteomeXchange dataset PXD078309
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ProteomeCentral Agent
May 13, 2026, 11:09:35 PM (5 hours ago) May 13
to ProteomeXchange
Dear ProteomeXchange subscriber, a new ProteomeXchange dataset is being announced. To see more information, click here:
https://proteomecentral.proteomexchange.org/dataset/PXD078309
Summary of dataset
Status: new
Identifier: PXD078309
HostingRepository: iProX
Species: Homo sapiens
Title: Repression of DNA Damage Response Sensitizes APL Cells to the Combined Genotoxicity of All-Trans Retinoic Acid and Arsenic Trioxide
Submitter: Landing Li
LabHead: Lei Li
Description: The synergistic combination of All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (ATO) has transformed acute promyelocytic leukemia (APL) from a terminal disease into a curable one. However, the molecular basis for the APL-specific synergy remains to be fully defined. In this work, we studied the mechanism that drives the unique efficacy of ATRA/ATO on APL cells. We found that the ATRA/ATO combination generates a high level of endogenous genotoxic stress, leading to exacerbated accumulation of DNA damage in APL cellular models and patient samples. Crucially, we found that ATRA-treatment triggers the ubiquitin-proteasome -mediated degradation of key DNA damage response proteins, including ATM and FANCD2. This APL-specific event is independent of PML-RARA turnover and creates a profound vulnerability to genotoxic stress, rendering APL cells more susceptible to the combined genotoxic stress from the ATRA-ATO combination. Our findings reveal that the synergized induction o
f genotoxic stress and the concurrent impairment of the DNA damage response mechanisms constitute a lethal "Double-Hit" that promotes APL-specific apoptosis. This study provides a novel paradigm for understanding therapeutic synergy and suggests that targeting DDR protein stability may extend the success of differentiation therapy to a broader range of leukemia.
HTML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD078309
XML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD078309&outputMode=XML
https://proteomecentral.proteomexchange.org/dataset/PXD078309
Summary of dataset
Status: new
Identifier: PXD078309
HostingRepository: iProX
Species: Homo sapiens
Title: Repression of DNA Damage Response Sensitizes APL Cells to the Combined Genotoxicity of All-Trans Retinoic Acid and Arsenic Trioxide
Submitter: Landing Li
LabHead: Lei Li
Description: The synergistic combination of All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (ATO) has transformed acute promyelocytic leukemia (APL) from a terminal disease into a curable one. However, the molecular basis for the APL-specific synergy remains to be fully defined. In this work, we studied the mechanism that drives the unique efficacy of ATRA/ATO on APL cells. We found that the ATRA/ATO combination generates a high level of endogenous genotoxic stress, leading to exacerbated accumulation of DNA damage in APL cellular models and patient samples. Crucially, we found that ATRA-treatment triggers the ubiquitin-proteasome -mediated degradation of key DNA damage response proteins, including ATM and FANCD2. This APL-specific event is independent of PML-RARA turnover and creates a profound vulnerability to genotoxic stress, rendering APL cells more susceptible to the combined genotoxic stress from the ATRA-ATO combination. Our findings reveal that the synergized induction o
f genotoxic stress and the concurrent impairment of the DNA damage response mechanisms constitute a lethal "Double-Hit" that promotes APL-specific apoptosis. This study provides a novel paradigm for understanding therapeutic synergy and suggests that targeting DDR protein stability may extend the success of differentiation therapy to a broader range of leukemia.
HTML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD078309
XML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD078309&outputMode=XML
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