Identifikation von Schlüsselgenen in der Pathogenese Myelodysplastischer Syndrome (MDS) mittels "high-density" Genomanalyse

• Applicant: Professor Dr. Daniel Nowak
• Subject Area: Hematology, Oncology
• Term: from 2007 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 50848630

• Final Report Year: 2010

Final Report Abstract

Zusammenfassend wurden mehrere Projekte zur Anwendung der hochauflösenden SNP Array Technik zur Untersuchung genomischer Veränderungen in hämatologischen Erkrankungen erfolgreich abgeschlossen und publiziert. Desweiteren konnte ich profunde Kenntnisse in der Methodik zur funktionellen Untersuchung von „target“ – Genen und Läsionen, wie z.B. die Anwendung retroviraler Expressionssysteme und Arbeiten im Mausmodell erlernen. Die gewonnenene Expertise werde ich zur verbesserten Diagnose und Erforschung hämatologischer Erkrankungen einsetzen.

Publications

• Differentiation therapy of leukemia – three decades of development Blood. 2009 Apr 16;113(16):3655-65. Epub 2009 Feb 12
  Nowak D, Stewart D, Koeffler HP
  
• Genome-Wide Mapping of Copy Number Variations Using SNP Arrays Transfus Med Hemother 2009;36:246-251
  Nowak D, Hofmann WK, Koeffler HP
  
• High density SNP array allelokaryotyping of human acute lymphoblastic leukemia (ALL) xenografts in immunodeficient mice reveals genomic changes upon in vivo induction of chemoresistance Onkologie 2009, Vol. 32, Suppl. 4, Abstract V389
  Nowak D, Hofmann WK, Papa R, Akagi T, Kawamata N, Thoennissen NH, Meixel A, Kato M, Sanada M, Ogawa S, Lock R, Koeffler HP
  
• Inactivation of Pre-B Cell Receptor-Mediated Tumor Suppression by Aberrant Splicing in Ph+ Acute Lymphoblastic Leukemia Blood 2009, Vol. 114, No. 22, Abstract #579
  Sprangers M, Klemm L, Nahar RR, Nowak D, Martinelli G, Hofmann WK, Koeffler HP, Jumaa H, Müschen M
  
• Molecular Allelokaryotyping of T-cell Prolymphocytic Leukemia (T-PLL) Cells with High Density SNP Arrays Identifies Novel Common Genomic Lesions and Uniparental Disomy (UPD) Haematologica. 2009 Apr;94(4):518-27. [Epub ahead of print]
  Nowak D, Le Toriellec E, Stern MH, Kawamata N, Akagi T, Dyer MJ, Hofmann WK, Ogawa S, Koeffler HP
  (See online at https://doi.org/10.3324/haematol.2008.001347)
• PAX5/TEL Exhibits a Dominant-Negative Role by Inhibiting the Expression of Genes Involved in BCR Signalling and Suppressing the Binding of Wild Type PAX5 to Its Direct Target Gene CD79A (mb-1) in a Human Pre-B ALL Cell Line Blood 2009, Vol. 114, No. 22, Abstract #3455
  Iwanski GB, Thoennissen NH, Lor, PY, Kawamata N, Nowak D, Fazio G, Biondi A, Gazzaniga G, Koeffler HP
  
• SNP array analysis of tyrosine kinase inhibitor (TKI) resistant chronic myeloid leukemia (CML) identifies heterogeneous secondary genomic alterations. Blood. 2009 Dec 2. [Epub ahead of print]
  Nowak D, Ogawa S, Muschen M, Kato M, Kawamata N, Meixel A, Nowak V, Kim HS, Kang S, Paquette R, Chang MS, Thoennissen NH, Mossner M, Hofmann WK, Kohlmann A, Weiss T, Haferlach T, Haferlach C, Koeffler HP
  
• The PAX5 fusion product PAX5-C20orf112 causes downregulation of pre-B cell receptor genes and induces differential proliferation patterns in B-lymphoblastic cell lines Blood 2009, Vol. 114, No. 22, Abstract #1284
  Nowak D, Kawamata N, Niebuhr B, Nowak V, Mossner M, Nahar RR, Thoennissen NH, Iwanski GB, Stocking C, Dugas M, Hofmann WK, Müschen M, Koeffler HP