A new study had identified a direct cooperation between two cancer genes which paves the way for targeted treatments, not only in Acute lymphoblastic leukemia but also in other leukemias where JAK3/STAT5 could have cooperated with HOXA9.

Acute lymphoblastic leukemia (ALL), the most commonly occurring cancer in children, with 100 new cases reported in Belgium every year. Despite the efficacy of chemotherapy in treating this disease, its long and short-term side effects are considerable.

The team of Prof. Jan Cools pursued this research project to learn more about how cancer genes interact with each other, with the goal of identifying alternative therapy options that don’t cause severe side effects.

An international group of researchers led by Prof. Jan of the VIB-KU Leuven Center for Cancer Biology have made a breakthrough in understanding the development of acute lymphoblastic leukemia, an aggressive cancer of the blood.

While scientists were already familiar with many cancer-causing genes and their separate functions, the VIB team has now illustrated how two cancer genes work together to trigger leukemia. Their insights are published in the scientific journal Cancer Discovery.

ALL have been caused by the accumulation of genetic changes (mutations) that alter the behavior of developing immune cells that transform them into aggressive leukemia cells. Recent studies have found that ALL cases were often characterized by mutations in a certain gene pathway, called JAK3 / STAT5.

The development of T-cell acute lymphoblastic leukemia (T-ALL) is a step-wise process via the accumulation of somatic mutations (36). While the study has identified and confirmed various important driver mutations in T-ALL, this has often been in the context of a single oncogene.

Cools said, "JAK3 / STAT5 mutations are important in ALL since they stimulate the growth of the cells, JAK3 / STAT5 mutations, frequent occurrence together with HOXA9 mutations."

In this study, Jan Cools and his team created a mouse model with cancer-associated JAK3 / STAT5 and HOXA9 mutations to determine if they cooperate to drive the development of ALL. HOXA9 mutations have a well-established role in leukemia development.

Dr. Charles de Bock VIB-KU Leuven said, "We examined the cooperation between JAK3/STAT5 mutation and HOXA9. We observed that HOXA9 boosts the effects of other genes, leading to tumor development. As a result, when JAK3/STAT5 mutations and HOXA9 are both present, leukemia develops more rapidly and aggressively. "

The team's identification of direct cooperation between these two genes paves the way for targeted treatments,  not only at ALL but also in other leukemias where JAK3 / STAT5 could cooperate with HOXA9.