’Dissecting PDGFRB function in NPM-ALK driven lymphoma’

Anaplastic large cell lymphoma (ALCL) is an aggressive form of a non Hodgkin’s lymphoma of T cell origin mainly found in children and young adults 1,2. The chromosomal translocation t(2;5)(p23;q35) of the NPM1 (Nucleophosmin) gene and the Anaplastic lymphoma kinase (ALK) generates an oncogenic fusion protein  (NPM-ALK) responsible for 50% of all ALCL cases in humans 3. The pathological NPM-ALK fusion product causes a constitutively active kinase activating a multitude of downstream signaling pathways such as RAS/ERK, JAK/STAT or PI3K/AKT/mTOR.

Recent evidence suggests that in addition to known cancer related signaling cascades, the family of AP-1 transcription factors plays a central role in lymphomagenesis and its subunits JUN and JUN-B are transcriptional targets of NPM-ALK 4,5. We have recently shown that JUN and JUN-B execute their key function in lymphoma development and progression by directly regulating the platelet-derived growth factor receptor B (PDGFRB) in a genetically engineered NPM-ALK lymphoma mouse model 6. Our data have furthermore far reaching consequences for clinical treatment strategies of NPM-ALK positive lymphomas in newly diagnosed as well as patients correlated to poor prognosis and low survival chances. Upon administration of the PDGFR inhibitor Imatinib (marketed by Novartis as Glivec), a patient refractory to conventional chemotherapy and relapsing after stem cell transplantation strikingly went into complete remission and is tumor free since early 2011 6.

Our research opened the doors to large cohort patient studies and represents an important step towards understanding the molecular mechanism of lymphoma development and progression.


Future directions and current projects


The main research focus of the Unit of Laboratory Animal Pathology lies in investigating the link between PDGFRB and lymphoma generation and dissemination. To this end we have generated mouse strains lacking the PDGFRB in the NPM-ALK model and dissect the contribution of PDGFRB to a malignant lymphoma phenotype by in vivo and in vitro methods.


  1. The interplay between tumor cells and tumor stroma
  2. The epigenetic component of lymphoma development
  3. The influence of DNA damage response and apoptosis to tumor progression




  1. Kadin, M. E. Ki-1/CD30+ (anaplastic) large-cell lymphoma: maturation of a clinicopathologic entity with prospects of effective therapy. J. Clin. Oncol. 12, 8847 (1994).
  2. Stein, H. et al. CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood 96, 368195 (2000).
  3. Morris, S. W. et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science 263, 12814 (1994).
  4. Mathas, S. et al. Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B. EMBO J. 21, 410413 (2002).
  5. Staber, P. B. et al. The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling. Blood 110, 337483 (2007).
  6. Laimer, D. et al. PDGFR blockade is a rational and effective therapy for NPM-ALK–driven lymphomas. Nat. Med. 18, 16991704 (2012).

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