Question

4.6 Fusion of the reading frames of the bcr and abl genes, as is often observed in cases of chronic myelogenous leukemia (CML), is an example of what type of genetic alteration

Answer 1

Answer:

The answer is reciprocal chromosomal translocation

Explanation:

The Philadelphia chromosome (Ph) is the truncated chromosome 22 generated by the reciprocal translocation t(9;22)(q34;q11) and was first identified in 1960 in a patient with CML [3]. Translocation of the proto-oncogene tyrosine-protein kinase (ABL1) gene located on chromosome 9 to the breakpoint cluster region (BCR) gene located on chromosome 22 results in a BCR-ABL1 fusion gene on the Ph [4, 5]. Three BCR-ABL1 fusion gene hybrids encode BCR-ABL1 protein isoforms p210, p190, and p230, which have persistently enhanced tyrosine kinase (TK) activity. These aberrantly activated kinases disturb downstream signaling pathways, causing enhanced proliferation, differentiation arrest, and resistance to cell death [6, 7]. Tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL1 protein are the most successful targeted therapy for Ph-positive leukemia.