in the bone marrow
The gene Ash1l plays a key role in regulating the maintenance and self-renewal of hematopoietic stem cells (HSCs), according to a study published in The Journal of Clinical Investigation.
The research provides new insight into how the body creates and maintains a healthy blood supply and immune system. It also opens new lines of inquiry about Ash1l’s potential role in cancers—like leukemia—that involve other members of the same gene family.
“If we find that Ash1l plays a role [in leukemia], that would open up avenues to try to block or slow down its activity pharmacologically,” said study author Ivan Maillard, MD, of the University of Michigan Medical School in Ann Arbor.
The Ash1l gene regulates the expression of multiple downstream homeotic genes, which help ensure the correct anatomical structure of a developing organism. And Ash1l is part of a family of genes that includes MLL1.
The researchers found that both Ash1l and MLL1 contribute to blood renewal. They observed mild defects in mice missing one gene or the other, but lacking both genes led to catastrophic deficiencies.
“We now have clear evidence that these genes cooperate to develop a healthy blood system,” Dr Maillard said.
He and his colleagues also found that Ash1l-deficient mice had normal numbers of HSCs during early development but a lack of HSCs in maturity—an indication the cells were not able to properly maintain themselves in the bone marrow.
Ash1l-deficient HSCs were unable to establish normal blood renewal after an HSC transplant. Moreover, Ash1l-deficient stem cells competed poorly with normal HSCs in the bone marrow and could easily be dislodged.
“By continuing to investigate the basic, underlying mechanisms [of blood renewal], we are helping to untangle the complex machinery . . . that may lay the foundation for new human treatments 5, 10, or 20 years from now,” Dr Maillard said.
