Gene Expression Sheds Light on More Aggressive Form of Leukemia

Research could lead to improved personalized therapies for acute myeloid leukemia.

The type of precursor cell in which a genetic alternation occurs plays a key role in setting which forms of acute myeloid leukemia (AML) are more aggressive than others.

“These so-called MLL fusion leukemias affect not only very young patients but also patients over 60 who have already undergone chemotherapy,” said lead researcher Juerg Schwaller.

Researchers used a mouse model to demonstrate how the genetic alteration that occurs in hematopoietic stem cells results in a particularly poor prognosis for AML. This form of the disease is highly aggressive, and found to be associated with chemotherapy resistance and extensive tissue infiltration.

Furthermore, researchers also discovered that the hematopoietic stem cells expressed certain genes that promote cell migration and tissue invasion; however, in later-stage precursor cells, they no longer expressed these genes.

“When we reduced expression of 1 of these genes in the early hematopoietic stem cells, disease progression was much milder,” said lead researcher Antoine Peters.

Researchers confirmed that these same genes were also expressed in humans when they applied the approach to samples collected from patients with aggressive AML.

“This prognosis thus depends on the particular hematopoietic stem or precursor cells in which the genetic alteration occurs, and what genes are expressed,” Peters said.

Authors noted that the expressed genes could also serve as future biomarkers.

“The expressions of genes such as EVI1, ERG, or ZEB1 now allows us to classify patients into different groups according to prognosis, and if necessary to adapt treatment,” Schwaller said. “Our findings should also enable us to develop new, more personalized therapies for these patients.”