High STAP1 expression in DUX4-rearranged cases is not suitable as therapeutic target in pediatric B-cell precursor acute lymphoblastic leukemia
| Autor: | Monique L. den Boer, Femke Stalpers, Valerie de Haas, Quirine J. Hartman, Marjolein Bakker, Elisabeth M. P. Steeghs, Judith M. Boer, Rob Pieters, Alex Q. Hoogkamer, Gabriele Escherich, Hester A. de Groot-Kruseman |
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| Přispěvatelé: | Pediatrics |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell Survival Fusion Proteins bcr-abl Receptors Antigen B-Cell lcsh:Medicine Antineoplastic Agents Biology Polymorphism Single Nucleotide Article 03 medical and health sciences Transcriptional Regulator ERG RNA interference Cell Line Tumor Precursor B-Cell Lymphoblastic Leukemia-Lymphoma hemic and lymphatic diseases Gene expression medicine Humans RNA Small Interfering lcsh:Science Gene B cell Adaptor Proteins Signal Transducing Cell Proliferation Chromosome Aberrations Homeodomain Proteins Gene knockdown Multidisciplinary lcsh:R breakpoint cluster region 3. Good health 030104 developmental biology medicine.anatomical_structure Cancer research RNA Interference lcsh:Q Signal transduction Signal Transduction |
| Zdroj: | Scientific Reports, 8:693. Nature Publishing Group Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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