Chromosomal translocation can cause leukemia

Contributed by: Alexia Adamo

 

Keywords

Animals, Cancer, DNA, Evolution, Fundamental research, Genes, Genetics, Historical figure, Lab, Medicine, Meiosis, Mendelian genetics, Molecular biology, Observational, Technology, Woman

 

Slides

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View and download in google slides here

 

Resources

Rowley, Janet. “Chromosomal translocations: revisited yet again.” Ash Publications, 15th September 2008 link

 

Notes

Slide 1: Researcher’s Background

Janet Rowley was an American Geneticist and the first scientist to identify a chromosomal translocation as a cause of leukemia and other cancers. Her continuing research in this area led to a better understanding of the pathogenesis, diagnosis, and treatment of cancer.

Biography in brief

Janet Davison Rowley (April 5, 1925 – December 17, 2013) was an American human geneticist and the first scientist to identify a chromosomal translocation as the cause of leukemia and other cancers.  Beginning at the age of 15, she finished the last two years of high school and the first two years of college in an advanced placement program, learning to think for herself and study independently. These skills were the ideal foundation for a research career.

Rowley remained at the University of Chicago and earned a bachelor of philosophy degree in 1944, a bachelor of science degree in 1946, and doctor of medicine degree in 1948.In 1962, after a year in England as an NIH trainee, studying the pattern of deoxyribonucleaic acid (DNA) replication in normal and abnormal human chromosomes, Dr. Rowley returned to the University of Chicago, as a research associate in the Department of Hematology. In the 70’s she doing research full time, and this is when she discovered the role of translocation in cancer. Rowley passed away in 2013, but her work and legacy lives on. 

Is (or was) their research under-valued because of their identity?

Yes

 

Are there other scientists/research examples that this example can replace or be added to?

Unknown

 

Slide 2: Research Overview

Take home message of study

Rowley was focused on genetics, specifically, trying to understand what genetic factors might lead to Leukemia. For a decade she used fluorescence microscopy and techniques of chromosome analysis to try and figure out how chromosomes in leukemia patients were different from healthy individuals’ chromosomes. She would stain and then photograph chromosomes of individuals with Leukemia and analyze them carefully. She noticed that the patients with leukemia had some abnormalities between chromosomes which differed depending on the type of leukemia. For example, Part of chromosome 21 had broken off and moved to chromosome 8, and part of 8 had moved to chromosome 21-aka a translocation. This discovery allowed major advancements in the overall knowledge and the treatment of cancer.

Study system

In the first image, we have depicted a fluorescence microscope. A fluorescence microscope uses fluorescence in order to identify certain properties of the organism of interest. In this case, Janet Rowley was able to use fluorescence microscopy to take images of the chromosomes she was analyzing. This allowed her to further analyze genetic makeup of an individual’s chromosomes. Next, we have an image of a karyotype which is being studied using the Q banding method. This goes hand in hand with fluorescence microscopy, since q banding is the method by which chromosomes are stained with “Quinacrine”. The patterns seen can be correlated with G bands of a chromosome. These 2 methods of study contributed most to Janet Rowley’s research and discoveries.

 

Slide 3: Key Research Points

Main figure

This represents the partial karyotypes that Rowley discovered from common chromosomal translocations. In her article she depicts how in the 1960s it was very hard to study chromosomes since there was limited technology given. Then a universal class of studying chromosomes came about in the 1970s i.e. Q-banding. In her research she applied this method to males showing 45 chromosomes to prove that the chromosome that they had lost due to their abnormal bone marrow was their Y chromosome. She was using 2 different samples with 46 chromosomes but missing 2 chromosomes that were replaced by two other groups. By using the Q-banding method, she noticed that both had an 8;21 translocation (top left of figure). Next, she had 2 patients with 48 chromosomes with 2 extra C group chromosomes. After her analysis she noticed that both of the patients had an extra chromosome 8. In addition to this, she identified a deletion in chromosome 22 and an extra chromosome 9 (seen top right of figure) and confirmed more translocations in these patients. With her continuous research on translocations in leukemia patients, by 1979 she was able to describe the 14;18 translocation (bottom right in figure) depicting that there are chromosomal differences in specific types of lymphomas. She was also able to discover that RARA was associated with t(15;17) (bottom left of figure). Therefore, to summarize, the contents of this figure is to depict which translocations and in which chromosomes were essential for her discoveries. 

 

Societal Relevance

The research that Janet did up until her death was outstanding. At the time when not much was known about cancer, her research shed light on what might be causing it. Identifying the cause allowed for further advancement in cancer research, development of medicine/drugs to treat cancer, and also could have influenced the technology used in order to answer the questions posed by a brilliant mind like Janet’s.