of the Max - MDC

Overexpression of the transcriptional repressor
activated B cell factor 1 (ABF-1) in HRS cells.
ABF-1 inhibits, in combination with the
inhibitor of differentiation 2 (Id2), the
B cell-specific gene expression program in
Hodgkin/Reed-Sternberg cells of classical
Hodgkin lymphoma. ABF-1 mRNA and protein
overexpression in HRS-derived compared to
non-Hodgkin cell lines shown in (A). ABF-1
mRNA expression analysis of primary HRS cells
by in situ hybridization is shown in (B).
A
B
from apoptosis. In addition, we showed that p53-dependent
apoptosis can be induced in HRS cells by the MDM2-antagonist
nutlin-3, and thus the activation of the p53 pathway
might represent a novel treatment strategy for cHL. These
data provide insights into the deregulated apoptosis and
survival signaling pathways in HRS cells.
Plasticity of neoplastic B cells in Hodgkin
lymphoma
Franziska Jundt, Özlem Acikgöz, Rolf Schwarzer, Ursula
Ellinghaus, Nina Mielke in collaboration with Lucio Miele
(Chicago, USA)
Our group is interested in molecular mechanisms which
might contribute to the plasticity of neoplastic B cells in
Hodgkin lymphoma. We are studying the role of Notch1
which is aberrantly expressed in Hodgkin and Reed-
Sternberg (HRS) cells. Notch1 is a receptor which is essential
for the maintenance of the stem cell pool and for cell
fate decisions in hematopoietic lineages. Subject of our
investigations is the function of aberrant Notch1 activity in
germinal center-derived HRS cells, which have lost the B
cell phenotype despite their mature B cell origin. The development
of B cells critically depends on a transcription factor
network. We showed that Notch1 disrupts the B cell-specific
transcription factor network by antagonizing B cell-specific
transcription factors and by inducing the expression of B
lineage-inappropriate genes. We demonstrated that Notch1
binds directly to the B cell commitment factor Pax5 and
aberrantly expressed Notch1 suppresses the B cell transcription
of E2A and EBF. Furthermore, we revealed that Notch1
induces the expression of activated B cell factor (ABF)-1.
124 Cancer Research