Discovering why young people are prone to certain kinds of cancer, relative to adults, reveals important insights about cancer that can benefit both groups. The fast-developing cells in a growing body differs from the development of cancer. Patricia Ernst, PhD, University of Colorado Cancer Center investigator and Professor of Pediatrics and Pharmacology at the University of Colorado School of Medicine is researching normal hematopoiesis (blood stem cell production) and how the production of leukemia occurs.

Patricia Ernst, PhD

“The features that differ between normal cells that are dividing rapidly in a young/developing person versus cells that have become cancerous are so similar and yet so fundamentally different,” Ernst says. Picking apart those differences will hopefully provide more insight into a treatment option that will kill the cancer cells without harming the healthy cells of the growing body.

The normal version of the MLL1 protein is essential for hematopoietic (blood) stem cell (HSCs) maintenance during late fetal development. It acts as a regulator for gene activity, affecting proteins, DNA and RNA to regulate its target genes. These target genes define the MLL1 molecular pathway and many of them play critical roles in stem cell self-renewal and in the production of leukemia.

MLL1 is altered by chromosomal abnormalities in human leukemia. Ernst says, “the gene MLL1 encodes a large protein that helps the survival and growth of normal blood cells. But, when this gene is broken, it can lead to rapid cell growth that can take over the bone marrow, blood and other organs.”

The work of the Ernst lab has shown that the mouse MLL1 gene is crucial for the development of blood cells. “HSCs lacking MLL1 can develop, but fail to acquire functional properties of adult HSCs,” says Ernst. “These developmental studies illustrate the critical roles of this pathway in vascular/blood cell development, which are being further pursued by identifying cellular functions and molecular pathways regulated by MLL1 during the development of the embryo.”

Researchers have begun to synthesize molecules that turn off MLL1. Work of the Ernst lab uses genetics to show the types of cancer that are predicted to respond to these molecules. Additionally, the Ernst lab is finding a way to create more healthy HSCs by modulating the normal MLL1 pathway so they can be transplanted into patients who lack these cells.

In the course of researching MLL1, the Ernst lab has begun studying a related gene, MLL2. This gene has been found to play a larger role in sustaining the viability of the leukemia cells, and yet it plays little role in normal production of blood cells, making it an excellent drug target. The next challenge is testing how broadly MLL2 plays a role in myeloid and lymphoid leukemias to determine where compounds that inhibit MLL2 would be beneficial.