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May 13, 2005Proceedings of the National Academy of Sciences

Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia

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Authors

PZPeizheng ZhengUniversity of Science and Technology BeijingKWKankan WangShanghai Jiao Tong UniversityQZQunye ZhangQilu Hospital of Shandong University

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Overview

Systems biology analysis uncovers coordinated differentiation and apoptotic networks in promyelocytic leukemia cells, highlighting mechanisms of retinoic acid and arsenic synergy.

Key Points

  • To identify the molecular networks and dynamic cellular responses underlying the synergistic therapeutic effects of retinoic acid and arsenic trioxide in acute promyelocytic leukemia.
  • Treated human acute promyelocytic leukemia NB4 cells with retinoic acid, arsenic trioxide, or their combination across a time series.
  • Profiled molecular responses using cDNA microarrays for transcriptome changes and two-dimensional gel electrophoresis coupled with mass spectrometry for proteome changes, integrated using computational biology tools.
  • Combination treatment induced coordinated regulatory networks that promoted granulocytic differentiation, induced cell-cycle arrest, and enhanced apoptotic sensitivity at both transcriptomic and proteomic levels.
  • Identified critical molecular events including the degradation of the PML-RARalpha oncoprotein, restoration of nuclear bodies, activation of the proteasome system, and stimulation of calcium and interferon signaling pathways.

Cite This Study

Zheng et al. (2005) studied this question.

synapsesocial.com/papers/6a0ab72e9b4eb2f7ce2e0740https://doi.org/10.1073/pnas.0502825102
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