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


DGAP-News: Alacris Theranostics GmbH / Key word(s): Study/Study
results
Alacris Theranostics GmbH: Basis for new treatment options for a fatal
leukemia in children revealed

29.07.2015 / 08:35

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Basis for new treatment options for a fatal leukemia in children revealed

Detailed molecular analyses allow new insights into the function of tumour
cells and options for new treatments

Berlin, 29th July 2015 - Acute lymphoblastic leukemia (ALL) leukemia is the
most common type of cancer in children. It can occur in various forms,
differing not only by specific changes in the genetic material of the
leukemia cells but also by their response to therapies. Now, an
international team of scientists from Berlin, Düsseldorf, Hannover,
Heidelberg, Kiel, and Zurich have succeeded in decoding the molecular
characteristics of an as yet incurable subtype of leukemia, paving the way
for new therapeutic approaches. Their results have been published in the
current issue of the journal Nature Genetics (27 July).

Although intensive research over the last decade has significantly improved
the survival rates of children suffering from ALL, a subset of patients
remains resistant to treatment. One example is the very aggressive and
incurable subtype associated with a t(17;19) chromosomal translocation,
which occurs due to breakage and aberrant fusion of genetic material in the
tumour cells, resulting in the formation of a new oncogenic protein encoded
by the genes TCF3 and HLF (TCF3-HLF-positive leukemia cells). Until now,
the molecular basis of this phenotype has remained elusive. An
international group of clinicians and scientists from different
universities and research institutions, with contributions from the
Berlin-based company Alacris Theranostics GmbH, has conducted an in-depth
analysis of the molecular features of the t(17; 19) ALL subtype.

The consortium team decoded the genome of the leukemic cells using
sophisticated bioinformatics methods. The team found genetic aberrations in
addition to the known translocation.  "We are glad that we could contribute
to this important project with genomic data analysis of leukemia cells to
unravel some of the molecular changes in this disease", says Bodo Lange
(CEO, Alacris Theranostics). With the aim of identifying therapeutic entry
points for this incurable form of ALL, the transcriptome of the cancer
cells was also analyzed in great detail, enabling identification of the
genes active within the leukemic cell. The so-called expression profile of
the cancer cells was deciphered by means of RNAseq, a focus of research in
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
acute lymphoblastic leukemia identifies recurrent mutation patterns and
therapeutic options. 27 July, 2015. Nature Genetics. doi: 10.1038/ng.3362.

About Alacris Theranostics GmbH

Berlin-based Alacris Theranostics (www.alacris.de), a spin-off company from
the Max Planck Institute for Molecular Genetics, develops new approaches in
personalized medicine for cancer patient diagnosis, treatment and drug
stratification. The company uses its systems biology modelling platform
ModCellTM to generate a "Virtual Patient" model, based on genome and
transcriptome data, obtained by next generation sequencing, alongside
information on complex pathways and from mutation and drug databases. The
"Virtual Patient" model can predict the effects of drug treatment as well
as optimized combinatory treatments to provide the means for truly
personalized medicine approaches. In addition, Alacris' "Virtual Clinical
Trial" system enables the in silico analysis of drug effects on patient
cohorts, thus identifying stratified patient groups with particular genetic
and molecular profiles that could be targeted by a drug to allow more
efficient drug development and approval.

 
# # #

Contact: 

Alacris Theranostics GmbH 
Dr Bodo Lange, CEO 
Fabeckstrasse 60-62 
D-14195 Berlin 
Germany 
Phone: + 49 30 8431 22 510 
Email: info@alacris.de 
www.alacris.de

MC Services AG 
Anne Hennecke, Managing Partner 
Tel.: +49 211 529 252 22
Email: anne.hennecke@mc-services.eu



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