In chronic myelogenous leukemia, white blood cells proliferate ceaselessly. In affected white blood cells, the BCR-ABL oncogene, the result of a gene fusion, transmits a constitutive growth signal. The severity of the disease correlates with the fraction of white blood cells that carry the BCR-ABL oncogene.

a) How does reciprocal translocation and fusion of the BCR and ABL genes lead to unregulated cell dIvision and leukemia

One treatment for the chronic myelogenous leukemia is a drug that inhibits the BCR-ABL protein and prevents it from transmitting the growth signal. This can result in remission of the disease by preventing proliferation of the cancer cells. During treatment of the disease, the effectiveness of treatment is monitored by assessing the level of the BCR-ABL oncogene present in a fixed quantity of white blood cells. Suppose that the structure of the DNA in the nonmutant BCR and ABL genes are as shown here, and that of the BCR-ABL oncogene is as depicted.

Short oligonucleotide primers that bind to the BCR and ABL genes as shown (the 3' end of each primers is at the tip of the arrow) are labeled 1, 2, 3, and 4.

b) How would you detect the presence of the BCR-ABL oncogene ?

c) If the drug is working, what would you expect to see ?