A 57-year-old woman has come to her physician to determine if something is seriously wrong with her as she has been suffering from fatigue, chronic headaches, and radiating pain and fullness on her left side for the past 5 months. Her physician orders a routine blood test that indicates the presence of increased immature white cells (blasts) that also contain the Philadelphia chromosome. This leads to a diagnosis of chronic myelogenous leukemia, CML. CML results from this translocation due to abnormal regulation of which of the following genes?

Question

Quizplus · Accepted Answer

The Philadelphia chromosome results from a translocation between chromosomes 9 and 22, leading to the formation of the BCR-ABL fusion gene. This fusion gene produces a constitutively active tyrosine kinase, which is responsible for the pathogenesis of chronic myelogenous leukemia (CML). Chronic myelogenous leukemia (CML) is a cancer associated with unregulated growth of myeloid lineage cells of the bone marrow which then accumulate in the blood. The affected cells are mature granulocytes (eosinophils, basophils, and neutrophils) and granulocyte precursors. Definitive diagnosis of CML is accomplished via the detection of a specific chromosomal translocation in metaphase cells. This translocation is referred to as the Philadelphia chromosome and its presence is denoted as Ph+. The Philadelphia chromosome results from a translocation between chromosomes 9 and 22 (t[9:22]). The t(9:22) translocation fuses the Abelson tyrosine kinase (ABL) on chromosome 9 with the BCR locus on chromosome 22. The BCR-ABL fusion protein results in constitutive activation of the tyrosine kinase activity of ABL. The normal function of ABL is to regulate the activity of a number of cell cycle- regulating proteins. Loss of regulated ABL activity therefore, leads to unregulated cell cycle progression leading to malignancy.

A 57-Year-Old Woman Has Come to Her Physician to Determine