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Far more than The Philadelphia Chromosome Story.
December 22, 2013 2:38 PM   Subscribe

On Tuesday, December 17th, 2013, Dr. Janet Rowley passed away. The story of her research and life serves as inspiration to Women Scientists, Men Scientists, Drug Developers and Urban Cyclists.

After receiving her M.D. in 1948, Dr. Rowley worked part-time through the 1950s-60s while raising four children. In 1961 she asked the director of the Argonne Cancer Research Hospital: “I have a research project started in England that I’d like to continue with. Could I work here part time? All I need is a microscope and a darkroom. And by the way, will you pay me? I must earn enough for a baby sitter.” And he said yes to everything!"

During this period she primarily worked at Karyotyping (or examining the chromosomes and their arrangement) of the nuclear DNA associated with various cancers. Through exacting visual examination of the micrographs of the chromatids of cancer patients, she determined the molecular basis of an aberration seen consistently throughout individuals with CML (Chronic Myelogenous Leukemia). While the gross phenotype of this aberration (a shortened Chromosome 22) was originally identified in 1959 and termed the Philadelphia Chromosome, Dr. Rowley used new fluorescent banding techniques to establish the cause of this chromosomal curtailing. In cells from 9 CML patients, she found that the missing piece of their Ch. 22 was in fact transposed to the arm of Ch. 9. Reciprocally, a small piece of Ch. 9 was now on Ch. 22.
While this finding, published in 1973, represented a previously unexplored molecular level of detail of the chromosomal phenotypes of cancer, it also provides the foundations for one of the most triumphant tales of cancer biology research and drug discovery.
In quick succession, Dr. Rowley and colleagues found other translocations associated with other Myeloid Leukemias, demonstrating that this was a more common mechanism in the etiology of leukemias and lymphomas.
In the case of the CML associated 22<—>9 translocation, subsequent decades of research has identified the exact oncogenic mechanism that arises as a consequence of the chromosome arm swaps. Briefly, in the translocated Philadelphia Chromosomes, an important cell cycle regulatory tyrosine kinase, ABL (Abelson murine leukemia viral oncogene homolog 1) that normally resides on Ch. 9, is fused to the BCR (Breakpoint Cluster Region) protein. This is not a perfect union of the two proteins, as the BCR-ABL fusion is lacking the auto-inhibitory, SH3, region of Abl. Thus uninhibited, the now constitutively active ABL kinase drives cell proliferation and genome instability in mature myeloid and progenitor cells.
With the oncogenic culprit identified by the early 90's, Drucker and colleagues where then able to screen libraries of small molecules in the search for candidate drugs that would inhibit the activity of the BCR-Abl fusion protein. Gleevec was discovered to be highly effective in physically blocking, and therefore inhibiting the activity of the Abl kinase domain. When given to CML patients, the drug is both incredibly effective and precise, in that it inhibits cell proliferation only in the cancerous cells carrying the fusion protein, and with drug treatment the 8 year survival rate improves to 95.2%.
Thus, thanks to Dr. Rowley's important, dedicated, and above-all patient work, thousands of patient's lives have been saved, and Gleevec remains an essential gold-standard of cancer therapies.

Never one to rest on her considerable laurels (Presidential Medal of freedom, Lasker, Albany medical etc). Dr. Rowley was a fixture on the UChicago campus, running an active research program even after being diagnosed with Ovarian Cancer in late 2010. On a bright pink bike, and always wearing a helmet, she was still making her way around the streets of Hyde Park until earlier this fall.

An admirable figure in all her parts, she will be greatly missed.
posted by Cold Lurkey (9 comments total) 16 users marked this as a favorite

 
After receiving her M.D. in 1948, Dr. Rowley worked part-time through the 1950s-60s while raising four children. In 1961 she asked the director of the Argonne Cancer Research Hospital “I have a research project started in England that I’d like to continue with. Could I work here part time? All I need is a microscope and a darkroom. And by the way, will you pay me? I must earn enough for a baby sitter.” And he said yes to everything!"

I'm daily reminded of the incredible effort women just slightly older than my mother had to make to pursue their own paths in life.

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posted by crush-onastick at 2:49 PM on December 22, 2013


“What I think is important is that young people take a very long view of their lives … Don’t be too impatient for things to all happen quickly, or think by the time you’re 35, that you’re over the hill. … I was 47 years old before I did anything that people would really look at twice. So, patience is an important aspect … and good luck. I have led, by and large, an extraordinarily lucky life.”

Helps when you're lucky and pretty obviously awesome.

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posted by MCMikeNamara at 3:06 PM on December 22, 2013 [2 favorites]


Good Lord, what an incredible human being.
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posted by Fibognocchi at 4:08 PM on December 22, 2013


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I had never heard of her before now, and this makes me sad.
posted by BlueHorse at 5:47 PM on December 22, 2013


I knew about the Philadelphia chromosome, but I didn't know about her.

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posted by hydropsyche at 6:27 PM on December 22, 2013


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posted by Bron at 9:41 AM on December 23, 2013


Woo yeah. She's terrific. Was, I mean. I don't mourn her, I celebrate her!
posted by Mister_A at 3:17 PM on December 23, 2013


My mom was disagnosed with Chronic Myelogenous Leukemia last year. My mom is a very smart woman (a lawyer), but utterly, utterly uninterested in science. Whereas I have a physics PhD. She usually drives me nuts with her fad diets and supplements, not to mention our disagreements about the efficacy of prayer and the reality of evolution.

So when she told me "I have cancer, but it's no big deal," I didn't exactly know how to take that. No big deal? "Yeah, I just have to take a pill." "A chemotherapy pill?" Because... Chemotherapy is pretty much always an intense experience, right? "No, it's this new pill, they cured my kind of cancer. Praise God!"

Praise Dr. Janet Rowley, I'd say.
posted by OnceUponATime at 8:31 AM on January 2 [1 favorite]


When she applied to medical school in 1942, she was accepted, but had to wait a year to enroll. Why? Because the med school told her that its quota for women—three out of a class of 65—was already filled!

Unbelievable.

This quote is awesome: “What I think is important is that young people take a very long view of their lives … Don’t be too impatient for things to all happen quickly, or think by the time you’re 35, that you’re over the hill. … I was 47 years old before I did anything that people would really look at twice. So, patience is an important aspect … and good luck. I have led, by and large, an extraordinarily lucky life.”

(From the "men scientists" link).
posted by OnceUponATime at 8:54 AM on January 2


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