Mutations in proteins called histone H1, which help package DNA in chromosomes, are a frequent cause of lymphomas, according to a study led by researchers at Weill Cornell Medicine, NewYork-Presbyterian and The Rockefeller University. The findings could lead to new approaches to treating these cancers.
Scientists in recent years have observed that mutations in histone H1 genes occur in lymphomas, but they have not known whether these mutations are causes or effects of malignancy. The study, which appears Dec. 9 in Nature, reveals that certain histone H1 mutations are indeed drivers of lymphoma, and promote these cancers by loosening areas of DNA that are normally tightly wrapped. This loosening allows aberrant expression of early development genes that are normally completely shut down in the mature lymphocytes from which lymphomas derive.
“It’s a very interesting set of findings that give us insights into the origins of lymphomas as well as the important role of histone H1 proteins in the maturation of cells,” said co-senior author Dr. Ari Melnick, the Gebroe Family Professor of Hematology and Medical Oncology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.
The other co-senior authors on the study were Dr. Ethel Cesarman, a professor of pathology and laboratory medicine at Weill Cornell Medicine and a pathologist at NewYork-Presbyterian/Weill Cornell Medical Center, and Dr. Alexey Soshnev, a postdoctoral associate in the laboratory of Dr. David Allis, the Joy and Jack Fishman Professor at The Rockefeller University.
Lymphomas are relatively common cancers. Each year around 85,000 people in the United States are diagnosed with them, and more than 20,000 people die of them. Most lymphomas arise from immune cells called B cells, which make antibodies.