The fusion occurs when the two get out of their normal positions on chromosomes inside a cell, a process called chromosomal translocation. BCR-ABL1 directs production of tyrosine kinease, which promotes a chaotic proliferation of white blood cells in the bone marrow. The leukemic cells migrate to the blood and invade the spleen, liver, brain, and other organs. When overwhelmed by these cells, the organs may stop functioning, and the risk of death becomes high. In Huettner's mice, the antibiotic tetracycline switches off the gene and its leukemia-producing activity.
Cancer cells stop reproducing and begin to die.
In this way, the life of a model leukemic mouse can be extended, but it can never be saved because the animal still carries the mutant gene. Tetracycline in mice and tyrosine kinease drugs in humans can inhibit generation of leukemia, but they don't eliminate BCR-ABL1. New tyrosine kinease inhibitors are now being tested on humans, but it remains to be proved that they can do the job alone. More effective treatments will probably involve combinations of the inhibitors with chemotherapy drugs, radiation, and bone marrow transplants. The Harvard mice offer unique advantages for doing these tests.