How to Stop Leukemia from Returning? Block β-catenin Pathway

Target stem cells to prevent leukemia’s return, Harvard scientists say. Usually, stem cells are seen as the “good guys,” and today, research into their regenerative properties is at an all time high. As the “building blocks” of the body that can go on to develop into blood, bone, brain and body organ tissues — they are seen as a potential renewable source of replacement tissues to treat many ailments for which there is no cure, or for which few treatments exist.

But where leukemia is concerned, stem cells are both the “good” and the “bad” guys. As the “good guys,” they are used in the bone marrow transplantation to treat this blood cancer.

But they are also the “bad guys” — leukemic stem cells are the very things that sustain this blood-forming disease, which affects about 245,000 Americans, and an additional 47,150 new cases that are expected to develop this year alone. Leukemic stem cells are also thought to be responsible for relapse — and 23,540 Americans are expected to die from the disease this year, according to the National Cancer Institute.

Thus, the eradication of these type of stem cells is believed to be the key to achieving the complete remission of leukemia.

Leukemia causes the blood-forming tissue in the bone marrow to produce large numbers of white blood that enter the bloodstream — crowding out normal blood cells and leading to anemia, bleeding and infections. Often, leukemia also spreads to the lymph nodes or other organs, causing swelling and pain.

Chronic myelogenous leukemia or chronic myeloid leukemia (CML) is one of four types of leukemias that progresses slowly and occurs mostly in children and in middle-aged adults.

In the case of 11-year old American, C.J. Banaszek, CML started with a nosebleed that lasted too long, prompting his mother to rush her son to the nearby Petaluma Valley Hospital, where he was diagnosed with CML in the early hours of Feb. 21.

His mom’s search for a bone marrow donor to match C.J.’s blood type has prompted her to embark on a mission to raise awareness about the importance — and relative ease — of donating bone marrow. This mission landed her and her son on the pages of the San Francisco Chronicle last April 7.

Meanwhile, C.J. has been out of school while he takes oral chemotherapy. He keeps busy reading, writing and constructing Lego sets at his Petaluma, California home while he waits to find a bone marrow match — his family believes that a bone marrow transplant is the only thing that will cure C.J.

Leukemia stem cells cause cancer to return
A pill called imatinib — known by its brand name Gleevec — is the first treatment for everyone with CML.
Sometimes, a chemotherapy medicine called hydroxyurea — marketed as Hydrea — is used temporarily to reduce the white blood cell count if it is very high at diagnosis.

The vast majority of CML patients taking drugs like imatinib go into remission — but often their cancer returns because lingering leukemia stem cells stubbornly resist these existing therapies.

New findings from Harvard researchers suggest that a combination approach to therapy is more effective and may stamp out CML for good. The researchers make their conclusions based on findings of their experiment on lab mice and publish these in the April issue of Cell Stem Cell.

“Imatinib inhibits the oncoprotein — that drives CML — and it is incredibly effective at putting patients into remission,” says Dr. Scott Armstrong, a prominent oncologist and hematologist who is co-director of the Harvard Stem Cell Institute Cancer Program and co-director of the leukemia program in the Dana-Farber Harvard Cancer Center. “But there is growing evidence that this doesn’t rid the body of the most immature cancer cells. The question is: How can we eradicate those cells?”