Inhibiting Leukemic Stem Cells

Blood cancers, also known as leukemias, are, in many ways, a disease of stem cells. A core of cancerous stem cells divide and produce progeny that overpopulate, overwhelm, and in some cases invade and destroy other tissues. However many cancer treatments are designed to specifically attack the progeny of the cancer stem cells and not the leukemic stem cells. Therefore, the disease is destined to relapse, since the main driving entities of the leukemia are left to flourish while their progeny have been killed off.

Acute myeloid leukemia or AML is largely a disease of older adults, and even though the survival rates have increased, only about one out of every four adult patients survives for five years after the AML has been diagnosed. The mean survival time for this disease, which predominantly occurs in the elderly, is less than a year for patients over 65 years. Younger adults tend to do much better than older people. For example, more than half (50%) of the people under 45 diagnosed with AML will live for at least 5 years, and some will be cured. But in others, however, the AML will return and there is no way to tell in advance who has been cured and who will relapse. In people over 65 years of age the outlook tends not to be so good and around 12 out of 100 people (12%) are alive for more than 5 years.

Relapses and treatment failure in AML is almost certainly due to leukaemic stem cells, which cannot be completely eliminated during treatment. However, researcher Dr. Marin Ruthardt from the Hematology Department of the Medical Clinic II and Dr. Jessica Roos, Prof. Diester Steinhilber and Prof. Thorsten Jürgen Maier from the Institute for Pharmaceutical Chemistry has discovered a chink in the armor of leukemic stem cells. They report their data in the current edition of the journal “Cancer Research.”

AML stem cells require an enzyme called 5-lipoxygenase or 5-LO in order to survive. 5-LO plays a very important role in inflammatory diseases like asthma. Ruthardt, Roos, Steinhilber, and Maier and the members of their research teams showed that the leukemic stem cells in a subgroup of AML could be selectively and efficiently attacked by chemical inhibitors of 5-LO. These inhibitors killed the leukemic stem cells in cell culture model systems and in leukemia mouse models.

“These results provide the basis for the potential implementation of 5-LO-inhibitors as stem cell therapeutic agents for a sustained AML cure, although this must be investigated further in preclinical and clinical studies in humans,” explains Dr. Ruthardt.

Prof. Maier continued: “In addition, there are plans for further molecular biological studies with the objective of understanding exactly how the 5-LO inhibitors act on the leukemic cells.”

Hopefully these inhibitors can be fast-tracked for Phase I studies in human patients, and if they prove safe under clinical conditions, then maybe, if all seems well, they can be used to treat AML patients with aggressive cancers that do not respond well to more traditional cancer treatments.