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LAPTM4B promotes AML progression through regulating RPS9/STAT3 axis.

Yongxiu Huang1, Meixi Peng2, Huanhuan Qin3

  • 1School of Medicine, Chongqing University, Chongqing 400044, China; Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.

Cellular Signalling
|February 9, 2023
PubMed
Summary

Lysosome-associated protein transmembrane 4 beta (LAPTM4B) is upregulated in acute myeloid leukemia (AML), promoting disease progression. Targeting LAPTM4B may offer a new therapeutic strategy for AML patients.

Keywords:
Acute myeloid leukemiaLAPTM4BProgressionRPS9STAT3

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Area of Science:

  • Oncology
  • Molecular Biology
  • Hematology

Background:

  • Acute myeloid leukemia (AML) presents a significant clinical challenge due to its heterogeneity and poor outcomes with current treatments.
  • Lysosome-associated protein transmembrane 4 beta (LAPTM4B) has been observed to be frequently upregulated in AML.
  • High LAPTM4B expression correlates with adverse prognostic indicators in AML patients.

Purpose of the Study:

  • To investigate the role of LAPTM4B in the progression of acute myeloid leukemia.
  • To elucidate the molecular mechanisms underlying LAPTM4B-mediated leukemia progression.
  • To evaluate LAPTM4B as a potential therapeutic target for AML.

Main Methods:

  • Analysis of LAPTM4B expression levels in AML patient samples.
  • In vitro and in vivo experiments to assess the functional impact of LAPTM4B on leukemia.
  • Co-immunoprecipitation assays to identify interacting proteins.
  • Western blotting and gene silencing techniques to study protein interactions and signaling pathways.

Main Results:

  • LAPTM4B was frequently upregulated in AML and associated with poor patient outcomes.
  • Overexpression of LAPTM4B enhanced leukemia cell proliferation and progression both in vitro and in vivo.
  • LAPTM4B was found to interact with RPS9, stabilizing its protein levels.
  • The LAPTM4B/RPS9 interaction led to the activation of STAT3, promoting leukemia progression.

Conclusions:

  • LAPTM4B plays a critical role in promoting acute myeloid leukemia progression through a RPS9/STAT3-dependent pathway.
  • LAPTM4B represents a novel and promising therapeutic target for AML treatment.
  • Understanding the LAPTM4B/RPS9/STAT3 axis offers new insights into AML pathogenesis.