Photo by Matthias Zepper
Researchers may have identified the cells responsible for MLL-AF4+ infant B-cell acute lymphoblastic leukemia, according to a paper published in Cell Reports.
The team analyzed mouse embryos and discovered a “window of opportunity” during which a pre-leukemic state can take hold.
They also found evidence to suggest this pre-leukemic state is driven by lymphoid-primed multipotent progenitor cells.
“One of the most common and aggressive types of infant blood cancer is associated with the MLL-AF4 fusion gene, which arises during pregnancy,” said study author Katrin Ottersbach, PhD, of the University of Edinburgh in the UK.
“One of the main impediments to improving the survival rates in infants is the lack of knowledge on where and when during development this mutation arises and how it affects the developing blood system of the baby.”
To gain some insight, Dr Ottersbach and her colleagues bred mice where one parent carries an inactive form of the MLL-AF4 fusion gene and the other parent expresses a gene for an enzyme that activates the fusion gene.
The embryos from this pairing entered a pre-leukemic state between days 12 and 14. The researchers found that MLL-AF4 imparted enhanced B lymphoid potential and increased repopulation and self-renewal capacity during this time.
Further investigation suggested that lymphoid-primed multipotent progenitor cells were the major contributors to the enhanced B lymphoid output and may therefore be the cells of origin.
The researchers noted that the mice did not actually develop infant leukemia, so more research is needed to identify the events required for progression to MLL-AF4+ infant B-cell acute lymphoblastic leukemia.
“Our findings reveal the first changes that take place in blood development caused by the MLL-AF4 mutation during a pre-cancerous state,” Dr Ottersbach said. “This has increased our knowledge on how this aggressive disease develops and will help identify early signs of disease and points for therapeutic intervention.”
