Alexander Burchardt

Detection of an activated JAK3 variant and a Xq26.3 microdeletion causing loss of PHF6 and miR-424 expression in myelodysplastic syndromes by combined targeted next generation sequencing and SNP array analysis

Myelodysplastic syndromes (MDS) are hematopoietic disorders characterized by ineffective hematopoiesis and progression to acute leukemia. In patients ineligible for hematopoietic stem cell transplantation, azacitidine is the only treatment shown to prolong survival. However, with the availability of a growing compendium of cancer biomarkers and related drugs, analysis of relevant genetic alterations for individual MDS patients might become part of routine evaluation. Therefore and in order to cover the entire bone marrow microenvironment involved in the pathogenesis of MDS, SNP array analysis and targeted next generation sequencing (tNGS) for the mostly therapy relevant 46 onco- and tumor-suppressor genes were performed on bone marrow biopsies from 29 MDS patients. In addition to the detection of mutations known to be associated with MDS in NRAS, KRAS, MPL, NPM1, IDH1, PTPN11, APC and MET, single nucleotide variants so far unrelated to MDS in STK11 (n=1), KDR (n=3), ATM (n=1) and JAK3 (n=2) were identified. Moreover, a recurrent microdeletion was detected in Xq26.3 (n=2), causing loss of PHF6 expression, a potential tumor suppressor gene, and the miR-424, which is involved in the development of acute myeloid leukemia. Finally, combined genetic aberrations affecting the VEGF/VEGFR pathway were found in the majority of cases demonstrating the diversity of mutations affecting different nodes of a particular signaling network as an intrinsic feature in MDS patients. We conclude that combined SNP array analyses and tNGS can identify established and novel therapy relevant genomic aberrations in MDS patients and track them in a clinical setting for individual therapy selection.

Four versus Two Years of Rituximab Maintenance (R-Maintenance) Following Bendamustine Plus Rituximab (B-R): Results of a Prospective, Randomized Multicenter Phase 3 Study in First-Line Follicular Lymphoma (the StiL NHL7-2008 MAINTAIN Study)

Mathias Rummel, MD, PhD, Christian Buske, MD, Bernd Hertenstein, MD, Christian Lerchenmüller, MD, Michael Koenigsmann, MD, Elisabeth Lange, MD, Manfred Reeb, MD, Ulrich Kaiser, MD, Christina Balser, Dirk Behringer, MD, Jan Dürig, Tobias Gaska, MD, Georg Maschmeyer, MD, Georg Schliesser, MD, Alexander C. Burchardt, MD, Juergen Barth, PhD, Frank Kauff, MD, Axel Hinke, PhD, and Richard Greil, MD Med. Clinic IV, Hematology, University Hospital Giessen, Giessen, Germany Comprehensive Cancer Center Ulm, Institute of Experimental Cancer Research, University Hospital Ulm, Ulm, Germany I. Medizinische Klinik, Klinikum Bremen-Mitte, Bremen, Germany Hematology and Oncology, Outpatient Clinic, Münster, Germany Outpatient Oncology Center, Hannover, Germany Evangelisches Krankenhaus Hamm, Hamm, Germany IDGGQ GbR, Kaiserslautern, Germany St. Bernward Hospital, Hildesheim, Germany Oncology, Practice for Oncology, Marburg, Germany Department of Haematology, Oncology and Palliative Care, Augusta-Kranken-Anstalt gGmbH Bochum, Bochum, Germany Department of Haematology, University Hospital Essen, Essen, Germany Hematology und Oncology, Brüderkrankenhaus St. Josef, Paderborn, Germany Klinikum Ernst von Bergmann, Potsdam, Germany Practice for Oncology, Giessen, Germany CCRC, Düsseldorf, Germany University Hospital Salzburg, Salzburg, Austria Corresponding author: mathias.rummel@innere.med.uni-giessen.de