Description:

The Department of Biochemistry & Molecular Genetics presents:

Naama Kanarek, PhD
Assistant Professor 
Department of Pathology, Boston Children's Hospital
Harvard Medical School

Presentation:

"Metabolic Vulnerabilities of Leukemia that Spreads to the Central Nervous System”

Abstract:

When pediatric acute lymphoblastic leukemia (ALL) develops in the central nervous system (CNS), the prognosis is often morbid. While the development of a therapy that effectively targeted CNS leukemia proved to be the most significant advance in pediatric ALL survival, this aggressive, intrathecally-administered treatment is often accompanied by neurocognitive side effects including both immediate and long-lasting deficits. In order to develop new drugs that specifically target ALL cells, even those in the CNS, there is a need to reveal ALL’s targetable vulnerabilities. Such vulnerabilities can be metabolic and stem from the harsh nutritional environment CNS leukemia cells face in the cerebrospinal fluid (CSF): their common site of proliferation. The CSF is nutritionally poor compared to the plasma, likely exposing CNS ALL cells to deprivation of some key metabolites, introducing metabolic vulnerabilities of ALL cells that reside in the CNS. 

Using an advanced genetic screen of what metabolic genes are essential for ALL growth in the CNS, we recently identified one such nutrient: the metal copper. These results, combined with our current follow up mechanistic in vitro and in vivo work suggest that copper essentiality is a vulnerability of ALL cells, systemically and in the CNS: Copper is 10-fold lower in the CNS compared to the blood, and can be potentially targeted pharmacologically with clinically-approved copper chelators. We therefore propose that copper is a promising target for therapy that will be able to tackle even the aggressive cancer cells that reside in the patient’s brain, and is a safe new strategy for targeting ALL without harming the patient’s quality of life at survivorship.  

Host: Dr. Issam Ben-Shara, Associate Professor of Biochemistry and Molecular Genetics