A team led by scientists at VIB, the Flanders Institute for Biotechnology, have shown how two cancer genes work together to trigger T cell acute lymphoblastic leukemia (ALL). The work was published recently in Cancer Discovery.
ALL is caused by an accumulation of mutations in the JAK/STAT signaling pathway that causes developing immune cells to transform into aggressive leukemia cells.
"JAK3/STAT5 mutations are important in ALL since they stimulate the growth of the cells. However, leukemia patients have additional gene mutations, and we found that JAK3/STAT5 mutations, frequently occur together with HOXA9 mutations," says Jan Cools at VIB-KU Leuven.
Jan Cools and his team created a mouse model with HOXA9 and cancer-related JAK3/STAT5 mutations. They then utilized molecular biology tools such as RNA-seq, ChIP-seq and ATAC-seq to see if the two mutated genes worked together to drive ALL.
"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," says Charles de Bock at VIB-KU Leuven.
The work lays ground and shows that HOXA9 does in fact help the JAK/STAT signaling pathway thrive. The team notes that their work will not only contribute to ALL research but other leukemias where there could be cooperation between these two genes.