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KWF awards €1.25 million to Princess Máxima Center researchers

The Dutch Cancer Society (KWF) has awarded two research projects from the Princess Máxima Center. The researchers receive €1.25 million in total for research into hereditary childhood cancer and acute lymphoblastic leukemia in infants.

Mutational patterns in hereditary childhood cancer

Although all forms of childhood cancer involve aberrations in the DNA, only in a few case there is a genetic predisposition. When a child is diagnosed with cancer, it is not always clear that it is caused by a mutation in the germline. However, such information could be relevant for treatment: a mutation may increase drug sensitivity of tumor cells. On the other hand, if the mutation is present in the germline (i.e. in all cells of the body) patients may be oversensitive to certain treatment, which could be life threatening.

To better recognize hereditary cancers, dr. Roland Kuiper, dr. Jarno Drost and dr. Ruben van Boxtel examine DNA mutation patterns. In hereditary childhood cancers, a single mutation can often cause a dysfunctional DNA repair system. ‘It can be more difficult to find a single causative mutation than the genome-wide effects on DNA changes’, says Kuiper, ‘the pattern of DNA damage can be used to recognize hereditary forms of childhood cancer.’

First of all, the researchers will track down the damage patterns. For this, they will use two approaches. First, they will analyze the genome of patients with a hereditary form of childhood cancer. Secondly, they will introduce the same mutations in organoid cultures and subsequently study the effects on DNA damage patterns. With the acquired knowledge the researchers will analyze big datasets to search for the patterns. Additionally, they will test existing and new medication on the organoid cultures.

Acute lymphoblastic leukemia in infants

Although acute leukemia has a favorable prognosis, this holds not true for infants with a translocation in the MLL-gene. The current treatment strategy seems to induce a strong reduction in leukemia at first. However, the high rate of recurrences shows that the treatment is not sufficient.

The last couples of years, dr. Ronald Stam and his team have been looking for better treatment options for this specific form of leukemia. Stam has screened thousands of compound on cell cultures. He wants to bring the drugs with favorable effects to the clinic. However, many steps need to be taken in between. To investigate the efficacy, safety and dose the researchers will test the drugs in mice, before they can be administered to children.