EWOG-MESRAT (European Working Group-Methylation Signatures and Response to Azacitidine Therapy; DRKS00007185) is an investigator-initiated trial that studied EPIC array-based DNA methylation patterns and next generation sequencing (NGS)-based variant allele frequencies (VAFs) of driver mutations in peripheral blood (PB) and bone marrow (BM) of 11 patients with newly diagnosed juvenile myelomonocytic leukaemia (JMML) during therapy with azacitidine. We demonstrate that the pharmacodynamic activity of azacitidine can efficiently be monitored in PB and BM. DNA methylation subgroup classification was linked to clinical response after three cycles of azacitidine and found to be conserved between PB and BM in all patients. In contrast, neither changes in VAFs nor changes in DNA methylation patterns during the course of therapy correlated with therapy outcome among the 11 study patients. This work thus supports the value of DNA methylation subgroup classification from PB samples for response prediction of single-agent azacitidine in patients with JMML.

Bristol Myers Squibb Summit New Jersey USA

Department of Paediatric Hematology and Oncology Charles University and University Hospital Motol Prague Czech Republic

Department of Paediatrics and Adolescent Medicine Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Pediatric Hematology and Oncology Faculty of Medicine Children's Hospital Medical Center University of Freiburg Freiburg Germany

Department of Pediatric Hematology and Oncology IRCCS Ospedale Pediatrico Bambino Gesu Rome Italy

Department of Pediatric Hematology and Oncology University Children's Hospital Münster Münster Germany

Department of Pediatrics and Adolescent Medicine University Medical Center Ulm Ulm Germany

Department of Pediatrics Catholic University of the Sacred Heart Rome Italy

Department of Pediatrics Frankfurt University Hospital Frankfurt Germany

Faculty of Medicine Institute of Medical Bioinformatics and Systems Medicine Medical Center University of Freiburg Freiburg Germany

German Cancer Consortium DKFZ Core Center Heidelberg Heidelberg Germany

German Cancer Consortium Partner Site Frankfurt Frankfurt Germany

German Cancer Consortium Partner Site Freiburg a Partnership between DKFZ and University Medical Center Freiburg Freiburg Germany

National Center for Tumor Diseases NCT Heidelberg a Partnership between DKFZ and Heidelberg University Hospital Heidelberg Germany

Pediatric Hematology Oncology Fondazione IRCCS Policlinico San Matteo Pavia Italy

Section of Translational Cancer Epigenomics Division of Translational Medical Oncology German Cancer Research Center Heidelberg Germany

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