Chromosomes: Lost in Philadelphia, Found in Chicago

Janet Rowley, MD, Blum Riese Distinguished Service Professor of Medicine, Molecular Genetics & Cell Biology and Human Genetics

Janet Rowley, MD, Blum Riese Distinguished Service Professor of Medicine, Molecular Genetics & Cell Biology and Human Genetics

A new book by science writer Jessica Wapner chronicles the history of what MIT’s Robert Weinberg, PhD, an authority on the genetic basis of cancer, calls the “poster child of rational drug development,” the long and twisted road to Gleevec.

Wapner traces the many steps from the recognition by Philadelphia cancer researchers in 1959 that patients with chronic myelogenous leukemia were missing part of chromosome 22, to the 1973 discovery by Chicago’s Janet Rowley, MD, that the missing piece was not lost, just misplaced.

It had been traded to chromosome 9 in exchange for a smaller bit of that chromosome. The exchange turned out to be lethal.

The book follows the many subsequent discoveries, and battles with drug companies, that eventually led to the breakthrough-drug imatinib, and when the disease learned how to get around that medication, to the sons of Gleevec, dasatinib, and nilotinib, and the grandson, ponatinib.

Wapner’s highly readable book “vindicates those who dreamed that one day cancers could be treated through rationally designed drugs—and in fact remains the major success story to this day,” Weinberg writes in the forward to the book. “The diagnosis of CML was once a death sentence.”

Now, CML diagnosed early can become a chronic disease, “never cured, strictly speaking, but kept in check.”

This book makes “good reading,” he adds, “for those interested in the work of the heroes who pushed this drug forward.”

Chicago readers should know that Rowley, the Blum Riese Distinguished Service Professor of Medicine, Molecular Genetics & Cell Biology and Human Genetics at the University of Chicago, first appears in chapter four.

About five pages are devoted to her early work linking the several chromosome translocations to specific forms of leukemia.

There is one mistake.

The book says she was the only woman in her class at medical school. In fact there were six, the medical school’s quota at the time.

Chapter eight opens with the work of Herb Abelson, MD, former chairman of pediatrics at the University of Chicago, who also served for six years as the associate dean and senior associate dean for admissions and student affairs at the University of Chicago Pritzker School of Medicine.

Abelson’s early work on what would become known as the Abelson virus led to the discovery of the role of tyrosine kinases in tumor growth.

The fusion protein Bcr/Abl that drives proliferation in patients with CML results from the abl gene moving from chromosome 9 to chromosome 22, where it merged with bcr – the defining feature of the Philadelphia chromosome.

A one-page pictorial version of the 300-page book is available here.

%d bloggers like this: