Rare Cases of Inheritance Offer Clues to Leukemia

As do most cancers, leukemia strikes sporadically. Though hereditary influences or environmental exposures may contribute to risk, its occurrence is usually considered random. For some rare families, however, the disease is hereditary. In only a few dozen known cases, parents pass it to their offspring as a single gene.

Dr. Marshall Horwitz, associate professor of medicine in the Division of Medical Genetics, studies rare genetic predisposition to leukemia and other blood cancers. Horwitz is attempting to map and identify the responsible genes.

Despite their rarity, hereditary cases are relevant to understanding the disease mechanism in the wider population.

“There’s value in identifying the genes that predispose to malignancy,” said Horwitz. “For one thing, they do contribute some portion of risk in the general population. They also give considerable insight into aspects of the disease’s natural history that are common to inherited and sporadic forms.”

In the case of solid tumor cancers that are partly hereditary, especially colorectal carcinoma, the genes passed down in mutated form through genetically predisposed families are the same genes sporadically mutated in the non-hereditary occurrences. The same is assumed true of the blood cancers Horwitz studies. Finding the abnormal genes in hereditary cases could help researchers understand the molecular genetic mechanism in all cases.

Horwitz studies blood samples taken from people who have the rare inherited forms of leukemia, lymphoma or bone marrow failure syndrome. Horwitz extracts the DNA from their blood, then scans all the chromosomes with genetic markers to try to find the chromosomal location of defective genes.

He then conducts a detailed gene search by sifting through that region of the genome. He looks for subtle differences in that genetic code compared to the genes of unaffected individuals.

Horwitz received both a Ph.D. in pathology and an M.D. at the UW. He completed his residency in internal medicine in 1992 and joined the faculty in 1995. Horwitz is an attending physician in general internal medicine and at the Medical Genetics and Family Cancer Genetics Clinic at UW Medical Center. He chairs the second-year course in genetics for medical students.

In 2002, Horwitz received a Presidential Early Career Award for Scientists and Engineers in recognition of his potential to unveil the mechanisms of inheritance in blood cancers.