Klin Padiatr 2011; 223 - A4
DOI: 10.1055/s-0031-1277065

Genome-wide associations of genetic variation with minimal residual disease in ETV6-RUNX1-positive childhood acute lymphoblastic leukemia

T Bartram 1, E Ellinghaus 2, R Panzer-Grümayer 3, G Cario 1, A Teigler-Schlegel 4, A Nebel 2, B Meissner 1, P Breithaupt 1, A Schrauder 1, P Nürnberg 5, M Zimmermann 6, S Schreiber 2, M Schrappe 1, A Franke 2, M Stanulla 1
  • 1Department of Paediatrics, University Hospital Schleswig-Holstein, Kiel, Germany
  • 2Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, Germany
  • 3St. Anna Children's Hospital and Children's Cancer Research Institute, Vienna, Austria
  • 4Oncogenetic Laboratory, Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Gießen, Germany
  • 5Cologne Center for Genomics, University of Cologne, Cologne, Germany
  • 6Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany

Aim: To assess the association of host genetic variation and early response to treatment as measured by minimal residual disease (MRD) in ETV6-RUNX1 fusion gene-positive childhood acute lymphoblastic leukemia (ALL) treated on protocol ALL-BFM 2000.

Methods: Genome-wide association analysis of 355,750 SNPs was performed in 311 patients demonstrating clearance of leukemic blasts from the bone marrow beyond measureable levels after induction therapy (<10-4 at treatment day 33) and 150 patients with still measurable MRD levels at this time point. The 38 most popular SNPs were selected, depending on an Odds Ratio of ≥4.0 or ≤0.15 and/or a p-value of <2.5×10-5, respectively, and were subsequently followed up in an independent cohort of ETV6-RUNX1-positive ALL cases exposed to the same treatment protocol.

Results: The Majority of the 38 most popular SNPs reside on or close to genes linked to regulation of apoptosis and signal transduction pathways. Results of the follow-up and the candidate SNPs as well as the conclusion will be presented at the meeting.