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Leukemia Stem Cell Research

Cancer stem cells in leukemia were first identified by researchers in 1994

Sean Morrison, Ph.D., former-director, Center for Stem Cell Biology in the University of Michigan's Life Sciences Institute, discusses leukemia stem cells.

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Because they have been studied the longest, scientists know more about leukemic cancer stem cells than they know about stem cells in other kinds of cancer. Cancer stem cells were first discovered in 1994, when University of Toronto researchers found them in acute myeloid leukemia. Within a few years, researchers identified cancer stem cells in other types of leukemia, as well.

Leukemia is a cancer of the blood or bone marrow. There are different types of leukemia, but they all start when something goes wrong with blood-forming cells in bone marrow, the spongy tissue inside bones. In leukemia, some of the cells created when these blood-forming cells divide are abnormal. They keep dividing uncontrollably, crowding out normal blood and immune cells we need to survive.

Some leukemias are more common in children; others usually develop in older adults. Without treatment, all leukemias can be fatal. The good news is that researchers have developed new anti-cancer drugs that can keep some leukemias in remission for years. In other types of leukemia, malignant stem cells can be killed with radiation and replaced with donated stem cells in a procedure called a bone marrow transplant.

But even when initial treatment is successful, leukemia often comes back. Scientists believe this is because even the most aggressive therapy does not kill all the cancer stem cells. To cure this type of cancer, scientists need a better understanding of what causes blood-forming stem cells to start behaving abnormally.

What makes cancer stem cells different from normal stem cells?

Sean Morrison, Ph.D. explains differences between cancer stem cells and normal stem cells in leukemia.

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Stem cell identity is determined by a complex mixture of cellular components - all of which are present individually in non-stem cells, too. It's the specific combination that is unique to stem cells. Many scientists believe mutations can transform normal stem cells or progenitor cells into cancer stem cells. The mutations that cause cancer act by enabling cancer stem cells to hijack normal stem cell self-renewal mechanisms and use them to multiply out of control.

Are all leukemias caused by cancer stem cells?

Many types of leukemia develop from cancer stem cells. In these cancers, a small subset of cancer stem cells can continue to grow and expand indefinitely, while most malignant cells divide for a limited period of time and then die.

What are blood-forming stem cells?

Sean Morrison, Ph.D. discusses hematopoietic stem cells and stem cell self-renewal.

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Hematopoietic, or blood-forming, stem cells are found in the bone marrow. These stem cells generate a fresh supply of new blood and immune cells to replace old, worn-out cells that are destroyed by the body. Stem cells give rise to partially restricted progenitor cells, such as myeloid and lymphoid progenitors. Myeloid progenitors generate red blood cells, platelets and a few other types of white blood cells. Lymphoid progenitors give rise to lymphocytes, or white blood cells that help the body fight infection and disease.

When a blood-forming stem cell divides, it uses a process called self-renewal to make one copy of itself and one progenitor cell. The new stem cell remains in a primitive, undeveloped state, but the new progenitor cell keeps dividing. Eventually, these progenitor cells give rise to all the different types of mature cells in blood and the immune system.

The body normally keeps tight controls on the process of self-renewal in stem cells. There's an elaborate network of tumor suppressor genes and other feedback mechanisms that slow down the self-renewal process and prevent it from happening too often.

In leukemia, however, the self-renewal process is out of control. Mutations that inactivate tumor suppressors or activate growth promoting signals allow malignant stem cells to disable or ignore the body's natural control mechanisms. It's like the cancer gets the go signals, but not the stop signals - as if the accelerator gets stuck in the "on" position -- and the stem cells make many more cells than the body can use.

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