UW Medicine Researchers Explore New Approaches to Treating Childhood Leukemia

By Thatcher Heldring

October 1, 2018

Acute lymphocytic leukemia (ALL) is the most common type of childhood cancer, representing approximately 25% of cancer diagnoses in children 0-15. More than 3,000 new cases of ALL are diagnosed every year in the United States – and the incidence rate is rising.

While the 5-year survival rate has increased significantly since 1975 (from 60% to 90% in patients under 15), treatment – typically chemotherapy, bone marrow transplants, and, recently, immunotherapy –  is still hard on children, families, and health systems, and can have side effects. Adolescents and adults fare less well.

Postdoc Matt Hart led the ALL research detailed in a new paper published in the journal PLOS Genetics

New research happening at UW Medicine points to a potential new approach to treating ALL. The multiyear investigation, led by postdoc Matt Hart in the lab of Marshall Horwitz at the Institute for Stem Cell and Regenerative Medicine, is the subject of a paper published recently by the journal PLOS Genetics.

ALL is a blood cancer that occurs when the bone marrow makes too many white blood cells known as lymphocytes. The rapid growth of these immature stem cells impedes the development of healthy immune cells, compromising the body’s ability to fight disease and infections.

The focus of the Horwitz lab centered on B-Cell lymphocytes. “About a third of all cases of B-Cell leukemia possess a mutation in the PAX5 gene,” says Dr. Horwitz. “Others have previously shown that restoring PAX5 can correct cell growth, but how to do that in ALL patients is not obvious. We do know that PAX5 is related to two other gene family members, PAX2 and PAX8, which are not mutated in leukemia. What we were able to show is that you can turn on PAX2 to functionally replace PAX5.”

The discovery opens up other, broader possibilities.

Dr. Horwitz and his team found that PAX2, which is normally activated by salt levels in the kidney, can similarly be switched on by adjusting salt concentrations for leukemia cells, a revelation that is leading to a new line of inquiry into the physiology of B-Cells, and, perhaps, new clues about how ALL begins – and how we can fight it.  Dr. Horwitz is also eager is to explore additional applications of using one related gene to compensate for another – not just for ALL, but for other types of cancer and genetic disease.

Could reprogramming stem cells at the genetic level someday eliminate the need for chemotherapy?  “That’s hard to say,” says Dr. Horwitz, emphasizing that this is an early stage investigation. “A colleague described it as a, ‘pipe dream’. But I think having a pipe dream is the basis for making discoveries.”