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Proteomic Profiling Identifies Specific Leukemic Stem Cell-Associated Protein Expression Patterns in Pediatric AML

Marianne Agerlund Petersen1,2, Carina Agerbo Rosenberg2, Marie Bill2

  • 1Pediatrics and Adolescent Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark.

Cancers
|July 27, 2022
PubMed
Summary

Researchers identified distinct protein profiles in pediatric acute myeloid leukemia (AML) stem cells and blasts compared to healthy controls. These proteomic differences highlight potential new biomarkers for developing targeted therapies for pediatric AML.

Keywords:
hematopoietic stem cellsmass spectrometrypediatric acute myeloid leukemiaproteomics

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Area of Science:

  • Proteomics
  • Pediatric Oncology
  • Hematology

Background:

  • Novel therapeutic strategies are needed for pediatric acute myeloid leukemia (AML).
  • Differences between leukemic and normal stem cells may offer therapeutic targets.
  • Understanding proteomic variations is crucial for developing targeted treatments.

Purpose of the Study:

  • To compare the proteomes of pediatric acute myeloid leukemia stem cells (AML-SCs) and blasts with healthy hematopoietic stem cells (HSCs).
  • To identify differentially expressed proteins that could serve as biomarkers for pediatric AML.
  • To explore potential therapeutic targets based on proteomic differences.

Main Methods:

  • Mass spectrometry was used to analyze protein expression.
  • Proteomes of AML-SCs and CLEC12A+ blasts from pediatric AML patients were compared to HSCs and hematopoietic progenitor cells from healthy controls.
  • Differential protein expression analysis was performed.

Main Results:

  • 456 shared proteins were identified in both leukemic and control samples.
  • AML-SCs and leukemic blasts showed distinct protein expression profiles, dissimilar to healthy cells.
  • Thirty-four proteins were differentially expressed between AML-SCs and HSCs, with notable upregulation of HSPE1, SRSF1, and NUP210.
  • Downregulation of EIF2 signaling suggested protein synthesis perturbations.
  • NUP210 and calreticulin were upregulated in CLEC12A+ blasts compared to HSCs.

Conclusions:

  • Significant proteomic differences exist between pediatric AML stem cells and healthy HSCs.
  • These findings support the exploration of AML-SC-specific biomarkers for novel pediatric AML therapies.
  • Identified protein expression variations offer potential targets for future therapeutic development.