The ability of a leukemic cell to remain in an immature state, capable of relentlessly propagating, has remained one of the vexing obstacles to the effective treatment of leukemia, particularly acute myeloid leukemia.
Rather than maturing, or differentiating, inside the blood-cell forming kitchen of the bone marrow, they grow and spread like wildfire, replacing the mature blood cells and leaving the body vulnerable to all manner of infectious disease and unchecked bleeding.
But researchers at UT Southwestern Medical Center have cracked the code to leukemia's prolific reproduction. They've identified an immune-system receptor protein that prevents these blood cancer cells from maturing, allowing them instead to multiply. "In our case, with the leukemia we study, we can probably try to either block the signaling of this receptor to keep the leukemia cells more differentiated, or have some way to destroy this receptor," Dr. Chengcheng "Alec" Zhang tells Unfair Park. "If we block the signalling of this receptor, then it kind of slows down leukemia."
So far, the use of certain chemicals to block these receptor proteins has been successful in hobbling leukemia's growth in studies involving mice, as detailed in the most recent issue of the journal Nature.
Their findings, however, may yield a second application. The same receptor protein that promotes the deadly replication of blood cancer cells also promotes the "stemness" of stem cells. Stem cells are currently used in the treatment of leukemia. A patient's immune system can essentially be stunned into submission with chemotherapy or radiation and rebooted with an infusion of healthy blood-forming stem cells. Keeping the stem cells from differentiating -- and thereby becoming useless -- while in culture is often difficult. "A major problem in the lab is that (the stem cells) differentiate too fast," Zhang says. "They lose their ability to replicate."
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This receptor protein could maintain their potency.