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Alacris Theranostics GmbH: Basis for new treatment options for a fatal leukemia in children revealed - Seite 2

Marie-Laure Yaspo's group at the Max Planck Institute for Molecular
Genetics in Berlin. The interplay between the fused TCF3-HLF oncogenic
protein, additional DNA changes and altered gene expression program leads
to a re-programming of leukemic cells to an early, stem-cell like
developmental stage, although the phenotypic appearance of the cells
remains similar. "This technique provides a quantitative read out of the
actual genetic program occurring in the cancer cells, which allowed us to
uncover relevant molecular mechanisms cooperating to promote tumorigenesis,
and to identify possible druggable targets. These findings could only be
achieved through analysis of the messenger RNAs", says Marie-Laure Yaspo.

In tandem, researchers from the team of Jean-Pierre Bourquin (University
Children's Hospital, Zürich) transplanted the leukemic cells in mice and
established a "humanised mouse model", an invaluable tool for testing
therapeutic response. The consortium team demonstrated that the mouse
engrafted and expanded cells retained most of the genetic features and
expression profiles of the original leukemic cells. The cells thus behaved
in a similar manner than in the patient, offering an attractive possibility
for translational medicine. The Zurich Group tested close to hundred drugs,
and demonstrated a very positive response of the mouse model
TCF3-HLF-positive cells to Venetoclax, a drug targeting the protein BCL2,
and which has already showed efficiency in other type of cancers.

The results of this study show the strong potential of coordinated research
between an international consortium and the use of new technologies for
advancing cancer research. This project was made possible through the
shared contribution of the research teams from Jean-Pierre Bourquin,
University Children's Hospital Zürich, Martin Stanulla, Hannover Medical
School, Arndt Borkhardt, Heinrich-Heine University, Düsseldorf, Jan Korbel,
European Molecular Biology Laboratory (EMBL), Heidelberg, Andre Franke,
Christian-Albrechts-University Kiel, and Marie-Laure Yaspo at the Max
Planck Institute for Molecular Genetics in Berlin. Contributions to the
genomic data analysis of leukemic cells came from the Berlin-based company
Alacris Theranostics. The project was funded by the German Federal Office
for Radiation Protection via the environmental research program of the
German Federal Environment Ministry and by the Swiss National Science
Foundation (SNF).

Original Publication:
Ute Fischer et al. Genomics and drug profiling of fatal TCF3-HLF−positive