The Origins of Leukemia

Leukemia origin in stem cells has genetic basis

May 14, 2012 / Author:  / Reviewed by: Chris Galloway, M.D.

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(dailyRx News) Leukemia can be very different from person to person, even within the same type of cancer. Scientists thought they understood how leukemia begins, but it may be more complicated than we thought.

Now published data on the immune systems of mice, which is nearly identical to humans, has flipped the main theory about leukemia's origin.

For years, researchers believed many differences in aspects of leukemia were due to which cells had turned cancerous, and when.

"Ask your doctor about genetic sequencing of your cancer."

Yet new data from a genetics lab working with the Medical University of Vienna showed that differences in leukemia are always the result of different genetic mutations, not the type of cell that went rogue, or when.

The study argues the importance of using genetic information in deciding the best cancer treatment, showing that ultimately chemotherapy needs to target more cells than previously thought in order to be successful.

While this new research highlights specific mutations, the main conclusion found that the differences between leukemias are the result of genetic mutations, not timing.

The research conclusively shows that two very different types of leukemia, chronic myelogenous leukemia and B-cell acute lymphoblastic leukemia, come from a mutation in the same type of cell, stem cells responsible for all blood production.

Published results from the study showed that one mutation in the human cell factories known as stem cells resulted in CML, and a different mutation results in B-ALL. These were thought to be two completely different spectrums of leukemia coming from two different types of cells, not one.

More importantly for the treatment implications, the research team lead by Dr. Kovacic found that the presence of certain molecular signals made by the immune system could guide a leukemia into forming different types.

Research showed that the presence of one cellular signal known as interleukin-7 meant that the leukemia would develop into the B-cell version.

Understanding the mechanics of the cancer formation is important to developing good therapies for leukemias.

Knowing the importance of interleukins in the development of cancers opens up a wide range of tools for oncologists to try, as future therapy could demonstrate that some aggressive kinds of leukemia may be able to be persuaded into changing into a milder form.

This adds to a growing trend of research that highlights the importance of knowing the exact genetics of a cancer in order to develop the best treatment for a patient.

While genetic sequencing of cancers are currently only done for some rare forms, in the near future it might very well become the most important step of the process.

Already the scientists behind the research have drawn conclusions about which directions to take in developing new plans for chemotherapy and leukemia treatment.

"A therapy that targets the bulk of tumour cells will not work," Dr. Kovacic explains.

"To treat B-ALL successfully, it will be necessary for us to learn much more about the development of the disease. A combined therapy is required, so future work should aim at developing drugs that target the long-term haematopoietic stem cells from which B-ALL is derived."

Results from the molecular research were published in the current issue of the journal EMBO Molecular Medicine. Authors stated no conflict of interest was present in the publication of their research.