High STAP1 expression in DUX4-rearranged cases is not suitable as therapeutic target in pediatric B-cell precursor acute lymphoblastic leukemia

Elisabeth M P Steeghs, Marjolein Bakker, Alex Q Hoogkamer, Judith M Boer, Quirine J Hartman, Femke Stalpers, Gabriele Escherich, Valerie de Haas, Hester A de Groot-Kruseman, Rob Pieters, Monique L den Boer

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Approximately 25% of the pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cases are genetically unclassified. More thorough elucidation of the pathobiology of these genetically unclassified ('B-other') cases may identify novel treatment options. We analyzed gene expression profiles of 572 pediatric BCP-ALL cases, representing all major ALL subtypes. High expression of STAP1, an adaptor protein downstream of the B-cell receptor (BCR), was identified in BCR-ABL1-like and non-BCR-ABL1-like B-other cases. Limma analysis revealed an association between high expression of STAP1 and BCR signaling genes. However, STAP1 expression and pre-BCR signaling were not causally related: cytoplasmic Igμ levels were not abnormal in cases with high levels of STAP1 and stimulation of pre-BCR signaling did not induce STAP1 expression. To elucidate the role of STAP1 in BCP-ALL survival, expression was silenced in two human BCP-ALL cell lines. Knockdown of STAP1 did not reduce the proliferation rate or viability of these cells, suggesting that STAP1 is not a likely candidate for precision medicines. Moreover, high expression of STAP1 was not predictive for an unfavorable prognosis of BCR-ABL1-like and non-BCR-ABL1-like B-other cases. Remarkably, DUX4-rearrangements and intragenic ERG deletions, were enriched in cases harboring high expression of STAP1.

Original languageEnglish
Article number693
Pages (from-to)693
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 12 Jan 2018

Keywords

  • Adaptor Proteins, Signal Transducing/antagonists & inhibitors
  • Antineoplastic Agents/pharmacology
  • Cell Line, Tumor
  • Cell Proliferation/drug effects
  • Cell Survival/drug effects
  • Chromosome Aberrations
  • Fusion Proteins, bcr-abl/genetics
  • Homeodomain Proteins/genetics
  • Humans
  • Polymorphism, Single Nucleotide
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
  • RNA Interference
  • RNA, Small Interfering/metabolism
  • Receptors, Antigen, B-Cell/metabolism
  • Signal Transduction
  • Transcriptional Regulator ERG/genetics

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