The co-occurrence of two gene mutations is linked to relapse in childhood leukemia

St. Anna Children’s Cancer Research Institute: New research discoveries facilitate future therapies

Leukemia, the most frequent cancer in children and adolescents, can be cured with modern chemotherapy in 80% of cases, indicating that up to 20% of the patients suffer a relapse and have an inferior prognosis. The causes for the re-occurrence of the leukemia have, so far, remained elusive.

Recently, the research group of Renate Panzer-Grümayer at St. Anna Children’s Cancer Research Institute has provided first evidence that the co-occurrence of two mutations is responsible for relapse. The study was performed in close collaboration with St. Anna Children’s Hospital and the Center of Molecular Medicine of the Austrian Academy of Sciences in Vienna, and with pediatric oncologists from Germany and Italy. Their study was published online on 28.4.2015 in the prestigious Nature Journal LEUKEMIA.

The mutations in question were detected by high sensitive Next Generation Sequencing methods and occurred especially frequently in relapsing cases. While the leukemia usually contains multiple populations of cells at initial presentation, the relapse leukemia often appears uniform, suggesting that the most resistant leukemic cells are in fact selected by the applied treatment. In their study the researchers found that two mutations frequently concurred at relapse and were linked with a resistance to therapy. This suggests that these mutant proteins are causally involved in relapse evolution and outcome.

Univ. Doz. Georg Mann, study head of Leukemia protocols in Austria: „These results are particularly exciting because of the availability of novel drugs specifically targeting these mutant proteins which could find their way into the clinic for the treatment of these patients. Therefore, researchers will test whether the deleterious effects of these mutations can be reversed by such inhibitors.”

The publication „KRAS and CREBBP mutations: a relapse-linked malicious liaison in childhood high hyperdiploid acute lymphoblastic leukemia“ was made possible by financial support from the Kapsch group, the Austrian Science Fund and the Austrian National Bank.