Perpetual AML Can Arise From Rare Leukemic Stem Cell

NEW YORK (Reuters Health) - A new study sheds light on why acute myeloid leukemia (AML) often recurs despite aggressive efforts to eliminate every last tumor cell. AML, scientists have learned, originates from a hierarchy of leukemic stem cell (LSC) classes that differ in both their action and in their ability to renew. A rare class of LSC has a high capacity for self-renewal, yet escapes cancer therapy by lying dormant during treatment.

"The existence of multiple stem cell classes shows the need for LSC-targeted therapies," Dr. John E. Dick and colleagues from the University of Toronto in Ontario write in the July issue of Nature Immunology.

In previous work, the researchers observed that not every leukemia cell has the ability to sustain leukemic growth. Only a rare group of cells, which they termed LSCs, have this capacity.

Building on this earlier work, in the current study the team tracked individual human LSCs serially transplanted into immune-deficient mice and discovered that not all LSCs are alike.

"Some LSCs functioned quickly after transplant to generate leukemic cells, but then these were lost because they lacked the ability to replicate themselves every once in a while as they divided," Dr. Dick told Reuters Health.

Other LSCs, he said, had a "high degree of replication and were able to produce leukemic cells for as long as we examined the transplanted mice. Moreover, we could passage these LSCs to additional mice and they continued to function."

As mentioned, the team also identified a class of LSCs that were persistently quiescent yet highly self-renewing. These particular LSCs did not become active until many months after the transplant and "thus would not be killed by therapies that kill dividing and proliferating cells," Dr. Dick explained. "The vast majority of anti-leukemia therapies in use kill cycling cells. Therefore our data explains why these therapies have not been very active for AML," he added.

Effective therapy for AML must be developed to target this LSC class that is responsible for "aggressively driving the growth and relapse of AML," the authors emphasize in their report.

Source: Nat Immunol 2004. [ Google search on this article ]

MeSH Headings: Biological Phenomena, Cell Phenomena, and Immunity : Biological Sciences : Biology : Cell Cycle : Cell Division : Cell Physiology : Cytogenetics : Genetics : Growth and Embryonic Development : Leukemia, Myelocytic, Acute : Physiological Processes : Tumor Stem Cells : Leukemia, Nonlymphocytic, Acute : Biological Sciences