Opportunities and challenges of proteomics in pediatric patients: circulating biomarkers after hematopoietic stem cell transplantation as a successful example

Proteomics Clin Appl. 2014 Dec;8(11-12):837-50. doi: 10.1002/prca.201400033. Epub 2014 Oct 30.


Biomarkers have the potential to improve diagnosis and prognosis, facilitate-targeted treatment, and reduce health care costs. Thus, there is great hope that biomarkers will be integrated in all clinical decisions in the near future. A decade ago, the biomarker field was launched with great enthusiasm because MS revealed that blood contains a rich library of candidate biomarkers. However, biomarker research has not yet delivered on its promise due to several limitations: (i) improper sample handling and tracking as well as limited sample availability in the pediatric population, (ii) omission of appropriate controls in original study designs, (iii) lability and low abundance of interesting biomarkers in blood, and (iv) the inability to mechanistically tie biomarker presence to disease biology. These limitations as well as successful strategies to overcome them are discussed in this review. Several advances in biomarker discovery and validation have been made in hematopoietic stem cell transplantation, the current most effective tumor immunotherapy, and these could serve as examples for other conditions. This review provides fresh optimism that biomarkers clinically relevant in pediatrics are closer to being realized based on: (i) a uniform protocol for low-volume blood collection and preservation, (ii) inclusion of well-controlled independent cohorts, (iii) novel technologies and instrumentation with low analytical sensitivity, and (iv) integrated animal models for exploring potential biomarkers and targeted therapies.

Keywords: Biomarkers; Graft-versus-Host Disease; Hematopoietic stem cell transplantation; Pediatrics; Risk stratification.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Biomarkers / blood
  • Biomarkers / metabolism*
  • Child
  • Graft vs Host Disease / blood
  • Graft vs Host Disease / diagnosis
  • Hematologic Diseases / blood
  • Hematologic Diseases / therapy
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Proteome / metabolism*
  • Proteomics / methods*
  • Transplantation, Homologous


  • Biomarkers
  • Proteome