Women that have helped in the fight against leukaemia

Probably the best known of all female scientists, Marie Curie was a Polish-French scientist who became the first ever woman to win a Nobel Prize, and remains the only woman to win two (for physics in 1903 and chemistry in 1911). She is famous for her studies of radioactivity, a term she coined herself.

As well as discovering the two elements radium and polonium, she was responsible for establishing the nature of radiation and how to isolate radioactive isotopes. From this, she and her husband, Pierre Curie, guided the first studies in the treatment of cancerous tumours by implanting small portions of radioactive material to help shrink them. This technique (called brachytherapy) is still used today for many types of cancers, including early stage breast cancer.

After Marie Curie’s discovery of radiation in 1903, it was swiftly adopted as a method of treatment for leukaemia. Before this, extremely few treatments existed, and the disease was almost always fatal. Many patients benefitted from Curie’s findings and so radiation therapy quickly became the default treatment for leukaemia for over half a century.

Sadly, the harmful effects of radiation were unknown at the time that Curie conducted her research and it is thought that constant overexposure to massive amounts of radiation in her lab contributed to her death from aplastic anaemia at the age of 66.

Gertrude Elion shared the Nobel Prize for Medicine in 1988 with colleagues George Hitchings and Sir James Black. Working alone and sometimes with her colleagues, Elion is famed for finding new drug treatments for a wide range of different diseases including gout, malaria, herpes and leukaemia. Elion and Hitchings observed fundamental differences in the way DNA is made between healthy cells and cancer cells to help them to create drugs that specifically targeted cancer.

Elion researched the use of organic compounds called purines, one of the building blocks of DNA. It was theorised by Hitchings that by stopping these purines from being incorporated into the DNA of dividing cancer cells they would stop growing. In 1950, Elion and Hitchings discovered the compound thioguanine which is used today to treat acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), and chronic myeloid leukaemia (CML). Elion successfully synthesised another purine-based compound called 6-mercaptopurine in 1957. Today both thioguanine or 6-mercaptopurine are valuable in the treatment of childhood leukaemia; when used in combination with other drugs, they are responsible for curing 80% of cases.

Janet Davidson Rowley was an American geneticist and Professor of Medicine at the University of Chicago. She was the first scientist to propose that certain chromosomal “translocations” are the cause of some cancers, including AML and CML. Chromosomal translocations are where specific regions of chromosomes switch places with parts of neighbouring chromosomes.

One day in 1972, while studying images of the chromosomes of a leukaemia patient, Rowley observed that large sections of two chromosomes had swapped places when compared to those of a healthy individual. The translocation noticed by Rowley is now known to be the “9;22” translocation of CML (seen in over 90% of CML cases) whereby the leukaemic cells all carry a translocation between chromosome 9 and chromosome 22 (also known as the Philadelphia Chromosome). The “8;21” translocation was discovered soon after which occurs in 5-10% of cases of AML.

Not only have new technologies enabled these translocations to be detected quickly to confirm a leukaemia diagnosis, but Janet Rowley’s findings have also led to a revolution in the treatments of these particular leukaemias. For example, a type of treatment for CML called Tyrosine Kinase Inhibitors (TKIs) – which works specifically by targeting the 9;22 translocation – has completely revolutionised the way the disease is managed, dramatically improving long-term survival in the majority of patients.

Jewel Plummer Cobb was an American biologist whose main field of research involved studying how skin pigment (melanin) can protect the skin from UV light. Part of this research included testing how chemotherapeutic drugs could stop cell division and be of potential use in the treatment of melanoma, a form of skin cancer that arises in the cells that create melanin.

Cobb eventually discovered that methotrexate was effective in the treatment of certain skin cancers and it was from this research that methotrexate was found to be effective against some types of leukaemia. For many years after this, methotrexate was adopted as the standard treatment for acute leukaemias.

Today, methotrexate remains FDA approved for people with ALL that has either spread or is at high risk of spreading to the central nervous system. As well as this, methotrexate is FDA approved for advanced cases of non-Hodgkin lymphoma.

Both Blackburn and Greider are involved in the research of telomeres. Every time our cells divide, the length of their DNA is shortened slightly, and it is telomeres (structures or “caps” at the end of all of our chromosomes) that act to prevent important genes from being chopped off each time our cells replicate. In 2009, Blackburn & Greider received the Nobel Prize for discovering an enzyme we produce that they called “telomerase”, which acts to maintain and rebuild these telomere caps.

In nearly all healthy cells, the enzyme telomerase is gradually produced less and less over time, causing the cells to eventually die. Blackburn & Greider discovered that in cancer cells, the production of telomerase never stops and so the cells are able to replicate indefinitely. The abnormal production of telomerase has been linked with the development of many leukaemias and research into this process has potential to lead to new targeted therapies.

Just this month, a new diagnostic test has been developed in Cardiff University (called “STELA”) which uses the length of these telomere structures to predict how quickly diagnosed patients with CLL will respond to the standard treatments. Since the standard treatment of chemotherapy is not always the most effective option for all CLL patients, a routine test such as this could improve the outcome for patients by making sure the most effective treatment is always given.