We've updated our Privacy Policy to make it clearer how we use your personal data.

We use cookies to provide you with a better experience. You can read our Cookie Policy here.

Advertisement
Basis for New Treatment Options for a Fatal Leukemia in Children Revealed
News

Basis for New Treatment Options for a Fatal Leukemia in Children Revealed

Basis for New Treatment Options for a Fatal Leukemia in Children Revealed
News

Basis for New Treatment Options for a Fatal Leukemia in Children Revealed

Read time:
 

Want a FREE PDF version of This News Story?

Complete the form below and we will email you a PDF version of "Basis for New Treatment Options for a Fatal Leukemia in Children Revealed"

First Name*
Last Name*
Email Address*
Country*
Company Type*
Job Function*
Would you like to receive further email communication from Technology Networks?

Technology Networks Ltd. needs the contact information you provide to us to contact you about our products and services. You may unsubscribe from these communications at any time. For information on how to unsubscribe, as well as our privacy practices and commitment to protecting your privacy, check out our Privacy Policy

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. 

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 JeanPierre 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-AlbrechtsUniversity 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).

Advertisement