Peptide microarray of pediatric acute myeloid leukemia is related to relapse and reveals involvement of DNA damage response and repair

Hasan Mahmud, Arja Ter Elst, Frank J G Scherpen, Tiny Meeuwsen-de Boer, Kim R Kampen, Valérie de Haas, Victor Guryev, Maikel M Peppelenbosch, Steven M Kornblau, Eveline S J M de Bont*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    5 Citations (Scopus)
    107 Downloads (Pure)

    Abstract

    The majority of acute myeloid leukemia (AML) patients suffer from relapse and the exact etiology of AML remains unclear. The aim of this study was to gain comprehensive insights into the activity of signaling pathways in AML. In this study, using a high-throughput PepChip™ Kinomics microarray system, pediatric AML samples were analyzed to gain insights of active signal transduction pathway. Unsupervised hierarchical cluster analysis separated the AML blast profiles into two clusters. These two clusters were independent of patient characteristics, whereas the cumulative incidence of relapse (CIR) was significantly higher in the patients belonging to cluster-2. In addition, cluster-2 samples showed to be significantly less sensitive to various chemotherapeutic drugs. The activated peptides in cluster-1 and cluster-2 reflected the activity of cell cycle regulation, cell proliferation, cell differentiation, apoptosis, PI3K/AKT, MAPK, metabolism regulation, transcription factors and GPCRs signaling pathways. The difference between two clusters might be explained by the higher cell cycle arrest response in cluster-1 patients and higher DNA repair mechanism in cluster-2 patients. In conclusion, our study identifies different signaling profiles in pediatric AML in relation with CIR involving DNA damage response and repair.

    Original languageEnglish
    Pages (from-to)4679-4690
    Number of pages12
    JournalOncotarget
    Volume10
    Issue number45
    DOIs
    Publication statusPublished - 23-Jul-2019

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