In industrialized countries like in Europe, acute lymphoblastic leukemia
is the most common form of cancer in children. An international
research consortium lead by pediatric oncologists from the Universities
of Zurich and Hannover has now succeeded in decoding a specific form of
this leukemia, which is regarded as incurable, and in obtaining insights
for new therapeutic possibilities.
Modifications of genes that control the development and promote the
growth of highly specific blood defense cells, so-called B-lymphocytes,
were evident in the leukemia cells studied. The interplay between the
pathogenic fusion of TCF3 with HLF and newly identified alterations
triggers a previously undetected reprogramming of the leukemia cells to a
very early, stem-cell-like developmental stage, which is not externally
visible on the cells. "This form of leukemia might be described as a
kind of 'wolf in sheep's clothing'," stresses Martin Stanulla. "These
key findings could be made, in particular, by reading out the messenger
molecules synthesized in the tumor cells,
a powerful technique allowing not only a deeper understanding of the
genetic program specifying the behavior of tumor cells, but also of
therapeutic entry points" adds Marie-Laure Yaspo.
Zurich researchers tested hundreds of novel drugs. Some of them, which
are still undergoing further clinical development, displayed a very
positive effect. One such drug is Venetoclax, which specifically targets
the protein BCL2 relevant for the programmed cell death and already
worked for other cancer strains.
The development of new courses of therapy in the humanized leukemia
model was supported by the Swiss National Science Foundation and the
University of Zurich's clinical research focus program "Human
Hemato-Lymphatic Diseases". The genetic studies were funded by the
German Federal Office for Radiation Protection via the environmental
research program of the German Federal Environment Ministry and by the
Max Planck Institute for Molecular Genetics.
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