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Olaf Heidenreich receives grant to target acute myeloid leukemia

For their studies into pediatric acute myeloid leukemia (AML), Olaf Heidenreich and Josef Vormoor have received a KiKa grant. With the 1.45 million euro they will be able to hire three team members to investigate how genetic variations in AML can be targeted in order to cure the patients.

Many cases of pediatric AML are caused by chromosomal rearrangements; very early in prenatal development a process goes awry. This results in a change in the structure of the chromosome, which holds DNA information. ‘Such a rearrangement is unique to cancer’, says Heidenreich.

‘Often several genetic aberrations have to pile up for a patient to get AML’, he explains, ‘the chromosomal rearrangement is always the first hit.’ In earlier studies and in collaboration with other international teams the Heidenreich lab has demonstrated that such rearrangements are also required for the leukemia to persist.

‘If cancer is the puppet, the chromosomal rearrangement is the puppet master’, explains Heidenreich. ‘If you destroy the puppet, the master will make a new one. But if you target the puppet master, the puppet becomes powerless.’  

Heidenreich’s ideas are ambitious; on the one hand he aims to directly target the chromosomal rearrangement with molecular scissors called small interfering RNA (siRNA). These are small pieces of RNA that can block the effects of the chromosomal rearrangements. That is, if the team manages to deliver the siRNA to the right location. For this they use lipid nanoparticles. ‘Let’s just call them magic bullets’, he simplifies.

In addition, Heidenreich and Vormoor search for disturbances of the molecular pathways that are a direct consequence of the chromosomal rearrangement. They aim to target these pathways with novel combinations of medicines. Heidenreich: ‘If we find the affected pathways and we know how to reach them, we may be able to cut the cords between the master and his puppet.’