'Matriarch of Modern Cancer Genetics,' Janet D. Rowley, MD, Helped Propel the Field of Molecular Oncology 

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Prior to this discovery, the Philadelphia chromosome had been thought to be a deletion. Showing that it wasn’t a deletion but was instead a translocation was a pretty major event.

—Janet D. Rowley, MD

Even as a child, Janet D. Rowley, MD, found the intellectual order and logic of science appealing. Born on April 5, 1925, in New York, Dr. Rowley’s parents, Hurford and Ethel Ballantyne Davison, moved the family to Chicago 2 years later. Both educators, the Davisons encouraged their only child in her academic pursuits, especially her interest in science.

Advanced Placement Program

When Dr. Rowley’s mother learned about an advanced placement program at the University of Chicago’s Hutchins College that combined the last 2 years of high school with the first 2 years of college, she helped her daughter apply for a scholarship. That event would prove to be the catalyst for a 7-decades-long association with the University of Chicago and alter the course of Dr. Rowley’s professional and personal life.

In 1940, at just 15, Dr. Rowley was awarded the scholarship, and earned a Bachelor of Philosophy degree in 1944. Two years later, she completed a Bachelor of Science degree and graduated from medical school in 1948. The following day, she married fellow medical student Donald Adams Rowley  and, after completing an internship in 1951, she began raising a family that would eventually include four sons.

Wanting to practice medicine only part-time while her children were young, Dr. Rowley spent three afternoons each week working in a variety of well-baby clinics. Later she worked in a Chicago clinic for children with mental disabilities, including Down syndrome, a genetic disorder caused by an extra chromosome. That experience would lead to a change in her professional focus from medicine to research and a lifelong study of the genetics of cancer.

“In 1959, the French pediatrician and geneticist Jérôme Lejeune reported that Down syndrome resulted from trisomy 21,” said Dr. Rowley. “My husband was going to England on sabbatical, and I couldn’t practice medicine there, so I decided I would learn cytogenetics at Oxford University. I got involved in a research project studying the pattern of deoxyribonucleic acid (DNA) replication in normal and abnormal human chromosomes. The field was so interesting, I decided I didn’t want to go back to work in the clinic and instead wanted to keep on doing research in chromosomes.”

Chromosomal Translocations

When Dr. Rowley returned to the University of Chicago in 1962, with the support of hematologist Leon Jacobson, MD, she continued work on her research project while obliging Dr. Jacobson, who asked Dr. Rowley to look at the chromosomes of his leukemia patients.

“The problem in the 1960s was that the method of staining chromosomes resulted in a uniform stain and you couldn’t tell one from the other except for a few that had distinctive sizes and shapes. All you could do was count and see whether there were 46 chromosomes, more than 46, or less than 46,” said Dr. Rowley.

By the early 1970s, a new chromosomal staining technique called banding came into use. With this method, metaphase chromosomes are treated with trypsin and  stained with Giemsa, or stained with quinacrine mustard, and then examined under a fluorescent microscope to analyze chromosomes for alternating light and dark stripes that appear along their length. The banding pattern allows the identification of chromosomal aberrations. (Today, molecular cytogenetic techniques such as fluorescence in situ hybridization [FISH] are often used to detect genetic abnormalities associated with cancer.)

Dr. Rowley learned the banding technique during her return trip to England while her husband was completing his second sabbatical at Oxford University. When she moved back to Chicago in 1972, Dr. Rowley used that knowledge to reexamine the slides of Dr. Jacobson’s patients with acute myeloid leukemia (AML) and found that chromosomes 8 and 21 were broken and had switched ends. It was the first discovery of a recurring chromosomal translocation in cancer.

Soon after, Dr. Rowley found a different translocation in the cells of patients with chronic myelogenous leukemia (CML). This time, one end of chromosome 22 was exchanged for a piece of chromosome 9, a translocation that results in the Philadelphia chromosome seen in CML.

“Prior to this discovery, the Philadelphia chromosome had been thought to be a deletion, and the biology was thought to involve a loss of DNA from the cell, with the missing genes on that DNA involved in regulating normal cell growth. Showing that it wasn’t a deletion but was instead a translocation was a pretty major event,” said Dr. Rowley.

Understanding the genetic abnormalities of CML eventually led to the development by Nicholas Lydon, PhD, and Brian Druker, MD, in the 1990s, of the tyrosine kinase inhibitor imatinib (Gleevec), which was approved by the Food and Drug Administration in 2001 for the treatment of CML.

In the late 1970s, Dr. Rowley identified a third translocation, the 15;17 translocation found in the rare disease acute promyelocytic leukemia (APL). This discovery convinced Dr. Rowley of the importance of translocations and helped her to solidify the consensus among scientists that cancer is a genetic disease.

Dr. Rowley has been the recipient of numerous awards, including the Albert Lasker Clinical Research Award and the National Medal of Science. In 2009, she received the Presidential Medal of Freedom, the nation’s highest civilian honor. In May, she was awarded the Albany Medical Center Prize in Medicine and Biomedical Research along with Peter Nowell, MD, for his work showing that a genetic defect could be responsible for cancer, and Dr. Druker for the development of imatinib. The three scientists will share the $500,000 award. Dr. Rowley’s portion will go to fund her five grandchildren’s college educations.

Early Fascination with Patterns

While Ethel Davison’s encouragement of her daughter’s academic pursuits and her doggedness in tracking down the scholarship that led to Dr. Rowley’s enrollment in Hutchin’s College at age 15 were instrumental in Dr. Rowley’s professional success, it was her father’s hobby of stamp collecting that developed the skills   contributing to Dr. Rowley’s later interest in deciphering the patterns in chromosomal aberrations in cancer.

“My father introduced me to stamp collecting when I was about 10 or 12 and while the stamps looked similar on the surface, there were subtle variations in the engraving or the watermarks, which make the stamps different. Studying those patterns taught me to pay close attention to patterns early on,” said Dr. Rowley.

Named the Blum-Riese Distinguished Service Professor of Medicine, Molecular Genetics and Cell Biology at the University of Chicago in 1984, the university further recognized Dr. Rowley’s scientific accomplishments with the establishment of the Janet Davison Rowley, MD, Professorship in Cancer Research in 2012.

Now, 88, Dr. Rowley interacts actively with colleagues in a laboratory in the Department of Medicine/Section of Hematology/Oncology at the University of Chicago, investigating the expression patterns of microRNA in leukemia cells. ■