October 22, 2007

Research points the way for custom cures ofintractable diseases
Human stem cells carrying leukemia are found to replicate consistently in mice blood,potentially leading to novel approaches for 'bespoke' disease treatments.
Your doctor discovers that you have the early stages of a potentially terminal illness, saya particularly intractable form of adult-onset leukemia. As per the long-standing plan,
your clone is deliberately given the disease, and while you head off to the tennis courts,
the doctors use your 'other' to determine the best therapy. In a few weeks or so, you
return to the hospital and begin the proven treatment for your specific illness, leaving
after several visits completely disease-free - perhaps with your clone for a nice set ofdoubles.
It is not a reality yet. At this moment in time, rodents are being substituted for humanclones. As part of a multi-institution global research project coordinated from the RIKEN
Research for Allergy and Immunology in Yokohama, cancer specialists are attempting
similar approaches using specially bred laboratory mice they inject with diseased
human blood stem cells cultivated in a lab dish. The early evidence is that this novel
approach to 'custom cures' may work.
The results of the cooperative study are being published this week in Nature
Biotechnology. Twelve separate research facilities and hospitals cooperated in the study,including Kyushu University in Japan, the Jackson Laboratory in Bar Harbor, Maine, andtwo research facilities at Harvard University.
While inducing the growth of human leukocytes in the bone marrow of lab animals has
been done before, this is the first reported instance in which human stem cells infestedwith acute myelogenous leukemia (AML) cells have been cultured and grown in a lab
dish, then found on injection to aggressively and consistently develop in the peripheral
blood cells of test animal recipients. The researchers expressed the belief that such'sleeper' cancer cells in the peripheral blood cells may be why leukemia can returnfollowing apparently successful cancer treatment. Human AML was maintained
cumulatively in vivo from the human donor in a series of mouse recipients for over one

year, demonstrating the long-term self-renewal capacity of leukemic stem cells.
The presence of circulating peripheral-blood AML cells, in addition to better reproducing
primary AML disease in vivo, allows the examination of a specific patient's AML cells
over multiple time points in a single lab mouse. In this way, the mice can serve as an
ideal vehicle for studying the mechanism of the disease and are potentially the bestmeans to counter it. As is often the case for patients with AML, in lab mice the effect of asingle round of treatment by a standard cancer-fighting drug can be transient, followedby a return of the disease in just a few weeks.
The ultimate significance of the study is the suggestion that instead of patients being
subjected to a battery of chemotherapy or radiation treatments to cure or arrest theirdisease, the less onerous alternative could be a few weeks of lab research on their
specific diseased cells that are reproduced in a lab dish then custom-cured in lab mice.
Ultimately, the single, most effective course of treatment would be selected from thelaboratory results. Then it becomes the patient's turn to be cured.
Original work:
F. Ishikawa, S. Yoshida, Y. Saito, et al., Chemotherapy-resistant human AML stem cells
home to and engraft within the bone-marrow endosteal region. Nature Biotechnology,Oct. 21, 2007

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