Rapid induction of a lymphoma-like disease in mice transplanted with NPM-ALK transduced bone marrow

Cornelius Miething, Renyuan Bai, Stephan W. Morris, Christoph Von Schilling, Burkhard Schmidt, Christian Peschel, Justus Duyster

Research output: Contribution to journalArticle

Abstract

A t(2;5) (p23;q35) chromosomal translocation can be found in a high percentage of anaplastic large cell lymphomas, fusing the nucleophosmin gene (NPM) on chromosome 5 to the anaplastic lymphoma kinase (ALK) on chromosome 2. The resulting fusion protein is a deregulated, constitutively active tyrosine kinase likely playing an important role in lymphomagenesis. Mouse models are an important step in delineating the contribution of single oncogenes to disease development. Recently, it was shown that a lymphoid malignancy can be induced in Balb/c mice with NPM-ALK transduced bone-marrow. Since lymphoma developed with a latency of more than 6 months, we tried to establish a mouse model with more rapid induction of NPM-ALK-induced lymphoma. Employing a modified infection/transplantation protocol utilizing a MSCV-based EGFP bicistronic vector allowing high expression in hematopoetic stem cells we induced a lymphoma-like disease in Balb/C mice within approx. 4 weeks. The mice succumbed to disease within a week after the first signs of the illness became apparent. The mice showed a marked pancytopenia in the peripheral blood with a massive infiltration of green fluorescent, NPM-ALK positive cells of the spleen, the bone marrow and some mesenterial lymph nodes. Cytologie examination revealed relatively large, immature cells of lymphoid appearance, which were negative for B- (B220) or T-(Thyl.2) cell markers in FACSanalysis. In conclusion, we describe the induction of a lymphoma-like disease with short latency in mice by transplantation with EGFP-NPM-ALK infected bone-marrow. This mouse-model may help to elucidate the role of NPM-ALK in lymphoma-induction and to develop new therapeutic options for this type of lymphoma.

Original languageEnglish (US)
Pages (from-to)93a
JournalBlood
Volume96
Issue number11 PART I
StatePublished - Dec 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Rapid induction of a lymphoma-like disease in mice transplanted with NPM-ALK transduced bone marrow'. Together they form a unique fingerprint.

  • Cite this

    Miething, C., Bai, R., Morris, S. W., Von Schilling, C., Schmidt, B., Peschel, C., & Duyster, J. (2000). Rapid induction of a lymphoma-like disease in mice transplanted with NPM-ALK transduced bone marrow. Blood, 96(11 PART I), 93a.