A rare incurable type of leukemia appears to be due to a mutant cell receptor that binds a signaling molecule closely if he is deaf to signals normally halt cell division. The researchers who discovered the mutant receptor hope the finding, reported in tomorrow's issue of Nature , can shed light on the most common forms of leukemia.
acute promyelocytic leukemia (APL) is an aggressive form of bone marrow cancer strikes about 3,000 people in the US each year. The problem starts when immune cells called leukocytes are divided and their two chromosomes fuse to create a mutant gene. Leukocytes then make a mutant receptor that can not fully respond to retinoic acid - a signal to a cell to stop dividing. Consequently, growth accelerates and becomes cancerous. In most cases, however, high doses of vitamin A - which produces retinoic acid - can slow the cancerous growth. But approximately 4% of patients do not respond to therapy.
To see why, a joint research team from the University of Pennsylvania Medical Center in Philadelphia and the European Institute of Oncology in Milan, Italy, analyzed the gene fusion in cell lines APL patients with incurable. They found that in these patients, the merger has a different mutant receptor. This receptor, it appeared, was a fatal affinity for a signaling protein called N-CoR that represses cell division. When the researchers added N-CoR in cells cultured with the rare mutant gene, the receptors bound so tightly that N-CoR failed to respond to retinoic acid and all the cells began to divide out of control . "Now we know the mechanism that causes APL, and we know why, in some cases, treatment can not," said team member Iris Zamir.
"There is a discovery intriguing, "says Thomas Waldmann, head of the metabolism of the National cancer Institute Management in Bethesda, Maryland. Although researchers have known for some time that retinoic acid treats leukemia, this research explains why. "It does not provide all the molecular details," says Waldmann, "but there is an opening" to discover future treatments.
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