A study by Bose and colleagues (1998. Blood 92: \(3362-3367\) ) and a previous study by Biernaux and others (1996. Bone Marrow Transplant 17: (Suppl.3) \(\mathrm{S} 45-\mathrm{S} 47\) ) showed that \(B C R-A B L\) fusion gene transcripts can be detected in 25 to 30 percent of healthy adults who do not develop chronic myelogenous leukemia (CML). Explain how these individuals can carry a fusion gene that is transcriptionally active and yet do not develop CML.

The BCR-ABL fusion gene is a rearranged gene formed as a result of a reciprocal translocation between chromosome 9 and chromosome 22, known as the Philadelphia chromosome. This fusion gene encodes an oncoprotein with constitutive tyrosine kinase activity, which leads to uncontrolled cell division and the development of CML in certain cases.

The transcriptional activity of the fusion gene refers to the process by which the genetic information encoded in the BCR-ABL fusion gene is converted into messenger RNA (mRNA) through transcription. The mRNA is then translated into the protein product, which in this case, is the oncoprotein with constitutive tyrosine kinase activity.

Though the presence of the BCR-ABL fusion gene is necessary for the development of CML, it is not always sufficient by itself. Other factors, like additional genetic mutations and epigenetic changes (changes to the DNA that affect gene activity without altering the DNA sequence), may be required for CML to develop. Furthermore, the body's immune system may also play a role in suppressing tumor formation in certain individuals.

Based on the understanding of the factors involved in the development of CML, individuals carrying the transcriptionally active BCR-ABL fusion gene may not develop CML due to the following reasons: 1. The fusion gene alone might not be sufficient to cause CML; additional genetic mutations or epigenetic changes may be required for leukemic transformation. 2. The individual's immune system may efficiently recognize and eliminate cells expressing the fusion gene, preventing tumor formation. 3. Variation in the activity and expression levels of the fusion gene can lead to different clinical outcomes, and some individuals may not develop CML despite carrying the active fusion gene. In conclusion, the presence of the transcriptionally active BCR-ABL fusion gene in an individual is not an absolute indicator that CML will develop, as additional factors play a role in the development of the disease.