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) S45–S47] showed that BCR-ABL 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 does not develop CML.

Verified step by step guidance

1. Step 1: Understand the nature of the BCR-ABL fusion gene. This gene results from a chromosomal translocation between chromosomes 9 and 22, creating the Philadelphia chromosome, which produces a constitutively active tyrosine kinase implicated in CML development.
2. Step 2: Recognize that the presence of the BCR-ABL fusion gene transcript indicates that the gene is transcriptionally active, meaning it is being transcribed into RNA, but this alone does not guarantee disease manifestation.
3. Step 3: Consider the concept of clonal expansion and additional mutations. For CML to develop, cells carrying the BCR-ABL fusion gene must undergo clonal expansion and acquire further genetic or epigenetic changes that promote uncontrolled proliferation and leukemogenesis.
4. Step 4: Explore the possibility of immune surveillance and cellular control mechanisms. Healthy individuals may have immune systems or cellular regulatory pathways that suppress or eliminate cells expressing the fusion gene before they can cause disease.
5. Step 5: Conclude that the detection of BCR-ABL transcripts in healthy adults likely reflects low-level, transient, or non-pathogenic expression of the fusion gene without the necessary secondary events or cellular environment required for CML development.

Key Concepts

BCR-ABL Fusion Gene and Its Role in CML

The BCR-ABL fusion gene results from a translocation between chromosomes 9 and 22, creating the Philadelphia chromosome. This fusion gene encodes a constitutively active tyrosine kinase that drives uncontrolled cell proliferation, a hallmark of chronic myelogenous leukemia (CML). However, presence of the gene alone does not guarantee disease development.

Clonal Expansion and Additional Genetic Events

For CML to develop, cells carrying the BCR-ABL fusion must undergo clonal expansion and acquire additional mutations or epigenetic changes. These secondary events promote malignant transformation and disease progression, explaining why some individuals with the fusion gene remain healthy without developing leukemia.

Gene Expression Regulation and Cellular Context

Although the BCR-ABL fusion gene may be transcriptionally active, its expression level, cellular environment, and regulatory mechanisms influence whether it causes disease. In healthy individuals, factors such as immune surveillance and controlled gene expression can prevent the fusion protein from triggering leukemogenesis.