Oncotarget

Research Papers:

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 and Eveline S.J.M. de Bont _

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Oncotarget. 2019; 10:4679-4690. https://doi.org/10.18632/oncotarget.27086

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Abstract

Hasan Mahmud1,2, Arja ter Elst2, Frank J.G. Scherpen2, Tiny Meeuwsen-de Boer2, Kim R. Kampen2, Valérie de Haas3, Victor Guryev4, Maikel M. Peppelenbosch5, Steven M. Kornblau6 and Eveline S.J.M. de Bont2

1 Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

2 Department of Pediatric Oncology/Hematology, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

3 Dutch Childhood Oncology Group, Stichting Kinderoncologie Nederland, The Hague, The Netherlands

4 Laboratory of Genome Structure and Aging, European Research Institute for the Biology of Aging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

5 Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands

6 Department of Stem Cell Transplantation and Cellular Therapy, University of Texas, MD Anderson Cancer Center, Houston, TX, United States

Correspondence to:

Eveline S.J.M. de Bont,email: edebont@elkerliek.nl

Keywords: AML; leukemia; peptide microarray; DNA damage and repair; signal transduction

Abbreviations: AML: acute myeloid leukemia; CIR: cumulative incidence of relapse; DCOG: Dutch Childhood Oncology Group; FAB: The French-American-British; WHO: World Health Organization

Received: February 07, 2019     Accepted: June 29, 2019     Published: July 23, 2019

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.


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