Ellington

It took UW professor Marshall Horwitz 19 years to get here.

A team of researchers from the United States and Australia began collecting data on families with a history of acute myeloid leukemia in 1992, and the U.S. portion of the study was conducted by Horwitz and his team of researchers. Nearly 20 years later, they found a mutation in the GATA2 gene, a gene that’s expressed in white blood cells. Those with the predisposed gene are also vulnerable to viral infections such as the human papillomavirus (HPV) and various immunodeficiency syndromes.

After seeing that the GATA2 gene count in the white blood cells was abnormally high in the families with a history of leukemia, Horwitz began to take a more careful look.

“It was clues,” Horwitz said about the process of looking specifically at the GATA2 gene. “They were educated guesses; that’s all they [were].”

For Horwitz, the motivation for delving into this research came from treating a leukemic patient who also had a family history. She was 21 years old and pregnant. Several of her family members also had leukemia in the past, which was why she was referred to Horwitz — a doctor who completed his residency in the field of genetics.

Horwitz then began the slow-and-steady process of research in hereditary leukemias, collaborating with Hamish Scott and Richard J. D’Andrea from the Centre for Cancer Biology at the University of Adelaide. Together, they identified both Australian and American families with a history of leukemia and collected a list of genes they thought might contain a predisposition. They sorted through more than 200 genes before they found something. The GATA2 gene is a transcription factor; after DNA is transcribed into RNA, the protein binds to the DNA. A mutated protein may cause an abnormal increase in white blood cells, leading to cancer in the blood: leukemia. The gene was identified in more than 20 families, and the Australian researchers said the gene may be more common than they anticipated. Horwitz calls the discovery “one small step forward” for leukemia research.

“Quite frankly, it was an overdue result. … It took a long time coming — longer than it should. It’s one more piece in the puzzle.”

Despite the excitement for his research, Horwitz sometimes doubted if he would ever get results, suspecting that the predisposed genes were difficult to identify.

“After working on it for nearly 20 years, … [I] began to give up hope,” Horwitz said. “Maybe the inheritance was not so straightforward; in many cases, the inheritance is quite complicated.”

Eventually, Horwitz got results. One of the immediate benefits of discovering the genetic predisposition to hereditary leukemias is for bone marrow transplants. While siblings have a one-in-four chance that they have matching bone marrow, they also have a 50-percent chance that, if they have the GATA2 gene, they have the same genetic predisposition as the leukemic patient.

“You wouldn’t want to donate a bone marrow that was destined to become leukemic, [and] we now have potential to screen bone marrow,” Horwitz said.

He said that, at the time they began the research on hereditary leukemias, the technology and ideas surrounding genetic research were progressing quickly.

“The ’90s [were] an exciting era in genes,” Horwitz said regarding the vast amount of progress made in genetic research that decade, starting with the Human Genome Project. “We thought that we could find genes for everything, and we’ve pretty much proven that we could find genes for everything.”

The Human Genome Project began in 1990, an effort to sequence the entire 20,000 to 25,000 DNA genes. It took the sequencing 10 years to complete at first, at a cost of about $3 billion. These days, the same job can be completed in two to three weeks at the price of $10,000.

Postdoctoral fellow Andrew Timms said technology continues to make strides in the field today. At the UW, a new DNA-sequencing machine was developed a few years ago that saved time and cost by sequencing only the “interesting” genes, Timms said — the genes that go on to make proteins and that offer clues to research on, for example, inherited forms of leukemia.

“It’s a really exciting time in genetics,” Timms said. “A lot of genes are [being discovered], genes that are affecting these people.”

Horwitz’s next step is to continue to try identifying genetic predispositions, looking at variations of cancer in the blood and pediatric disorders. Horwitz said the quality of research currently being done at the university, in all departments, offers undergraduate students an advantage to their education.

“If you take a science class, or almost any class at the UW, the professor is going to be actively engaged in research,” Horwitz said. “Most faculty consider themselves researchers.”

The UW consistently ranks among the top universities funded for research; last year, the UW was only second to Johns Hopkins University for federal funding received, and the university has received a total of more than $1 billion.

“You can take courses from people who are actually creating the knowledge you hear about, … rather than just having a professor who’s recapitulating work that other people have done,” Horwitz said. “You hear it straight from the horse’s mouth.”

Reach Features Editor Hayat Norimine at features@dailyuw.com.