Damon Runyon Cancer Research Foundation

Scott A. Armstrong, MD, PhD (Damon Runyon-Lilly Clinical Investigator '03-'08) and colleagues at the Children's Hospital, Boston, and the Dana-Farber Cancer Institute, Boston, identified a novel mechanism that underlies a form of acute lymphoblastic leukemia (ALL) known as MLL-AF4.  This form of disease makes up 70 percent of ALLs striking infants, who suffer rapid relapses and are cured at a rate of under 50 percent with chemotherapy.  Using a new mouse model of MLL-AF4, they found that the defective protein (also called MLL-AF4) giving rise to the disease abnormally modifies a histone protein; this alters chromosome structure and results in gene activation and initiation of leukemia.  In these studies, the researchers also identified an enzyme called DOT1L, which acts in partnership with MLL-AF4.  Enzymes like DOT1L can be targeted with small-molecule drugs, resulting in inhibition of critical genes that contribute to malignancy.  In general, reversal of histone modifications could be an important therapeutic approach for a variety of cancer types.  This work was published in the journal Cancer Cell.

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Maura L. Gillison, MD, PhD (Damon Runyon-Lilly Clinical Investigator '00-'05) of The Johns Hopkins University School of Medicine, Baltimore, and colleagues reported the results of the first comprehensive epidemiological study of human papillomavirus (HPV)-associated cancer data in the US.  In an analysis of data from 1998-2003, they identified 25,000 cancer cases per year at cancer sites associated with HPV infection.  Of these, the researchers determined that HPV infection is the underlying cause of 80% or 20,000 of the cancers.  These findings, which were reported in a Centers for Disease Control and Prevention (CDC) monograph, suggest a growing need for HPV vaccination in both women and men for cancer prevention.  In a second study published in the journal Clinical Cancer Research, Dr. Gillison and team demonstrated that simple "swish and spit" saliva rinses are able to detect oral HPV infection in patients and that this infection is more frequent in those with HPV-positive head and neck cancer.  This represents a simple way to monitor HPV infection over time to identify those at risk of developing cancer or cancer recurrence.

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