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Researchers from the Department of Pediatrics and Adolescent Medicine and the Institute of Experimental Pediatric Hematology and Oncology identify potential therapeutic targets in the non-coding part of the leukemia genome

Prof. Dr. Jan-Henning Klusmann and Prof. Dr. Dirk Heckl

A new study led by Prof. Dr. Jan-Henning Klusmann and Prof. Dr. Dirk Heckl identifies and characterizes the MYNRL15 DNA region (locus), and provides significant new insights into the essential role of the non-coding genome in myeloid leukemia.

The classical view of the genome considers only 2% of its total size, i.e. the protein-coding region. However, according to the current state of the art the remaining, non-coding 98% is also highly active and thus plays a crucial role in the development and behavior of cells. This non-coding part is largely unexplored on the functional level, especially with respect to the development of acute myeloid leukemia (AML).

In a comprehensive study based on detailed mapping of non-coding RNAs in healthy and malignant cells in combination with functional genomics, the Klusmann and Heckl labs have gained highly interesting new insights into the role of these non-coding RNAs and their underlying genomic origin. Particularly striking was the MYNRL15 locus, which selectively regulates the survival of myeloid leukemia cells while its perturbation does not affect healthy cells. Mechanistic studies revealed how the MYNRL15 locus controls the vital functions of leukemia cells via 3D regulation of the genome, and showed how interfering with these cellular functions may lead to the future development of novel and highly promising therapies.

Beyond the scientific findings, the study underlines how basic translational research leads to a better understanding pediatric leukemias and the development of targeted therapies by combining the complementary expertise provided by the pediatric oncology focused Institutes and Departments of the Goethe University Frankfurt.

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