# Chromosomal Translocation Activating Oncogenes: Two Mechanisms ## Step 1: Altering Structure — Philadelphia Chromosome in CML **Explanation:** In chronic myeloid leukemia (CML), a specific chromosomal translocation, t(9;22)(q34;q11), creates the Philadelphia chromosome. This translocation fuses the BCR gene from chromosome 22 with the ABL gene from chromosome 9, resulting in a novel BCR-ABL fusion gene. - The fusion gene encodes a constitutively active tyrosine kinase, which continuously signals for cell proliferation and survival, leading to cancer. **Summary:** The Philadelphia chromosome activates the oncogene by creating a chimeric protein with new, harmful activity. --- ## Step 2: Altering Abundance — Burkitt's Lymphoma **Explanation:** In Burkitt's lymphoma, a translocation commonly involves chromosomes 8 and 14 [t(8;14)(q24;q32)]. Here, the MYC oncogene from chromosome 8 is placed near the highly active immunoglobulin heavy chain (IgH) promoter/enhancer on chromosome 14. - This causes overexpression of the normal MYC protein, driving uncontrolled cell division. **Summary:** Burkitt's lymphoma activates the oncogene by increasing the amount of a normal growth-promoting protein. --- ## Final Answer - **Philadelphia chromosome in CML:** Activates an oncogene by altering the protein’s structure, creating a new, constitutively active fusion protein (BCR-ABL). - **Burkitt's lymphoma:** Activates an oncogene by increasing its abundance, leading to excessive MYC protein due to proximity to a strong enhancer. Both mechanisms show how chromosomal translocations can lead to cancer by either changing how an oncogene works or how much of it is made.