As a result, part of the BCR ("breakpoint cluster region") gene from chromosome 22 is fused with the ABL gene on chromosome 9. This abnormal "fusion" gene generates a protein of p210 or sometimes p185 weight (p210 is short for 210 kDa protein, a shorthand used for characterizing proteins based solely on size). Because abl carries a domain that can add phosphate groups to tyrosine residues (a tyrosine kinase), the bcr-abl fusion gene product is also a tyrosine kinase. The fused BCR-ABL protein interacts with the interleukin 3beta(c) receptor subunit. The BCR-ABL transcript is continuously active and does not require activation by other cellular messaging proteins. In turn, BCR-ABL activates a cascade of proteins that control the cell cycle, speeding up cell division. Moreover, the BCR-ABL protein inhibits DNA repair, causing genomic instability and making the cell more susceptible to developing further genetic abnormalities. The action of the BCR-ABL protein is the pathophysiologic cause of chronic myelogenous leukemia. With improved understanding of the nature of the BCR-ABL protein and its action as a tyrosine kinase, targeted therapies (the first of which was imatinib) that specifically inhibit the activity of the BCR-ABL protein have been developed. These tyrosine kinase inhibitors can induce complete remissions in CML, confirming the central importance of bcr-abl as the cause of CML. Diagnosis
CML is often suspected on the basis of a complete blood count, which shows increased granulocytes of all types, typically including mature myeloid cells.
Arcus senilis (AS), also known as gerontoxon, arcus lipoides, arcus cornae, corneal arcus, arcus adiposus, or arcus cornealis, are rings in the peripheral cornea. It‘s usually caused by cholesterol deposits, so it may be a sign of high cholesterol. It is the most common peripheral corneal opacity, and is usually found in the elderly where it is considered a benign condition. When AS is found in patients less than 50 years old it is termed arcus juvenilis. The finding of arcus juvenilis in combination with hyperlipidemia in younger men represents an increased risk for cardiovascular disease. Pathophysiology
AS is caused by leakage of lipoproteins from limbal capillaries into the corneal stroma. Deposits have been found to consist mostly of low-density lipoprotein (LDL). Deposition of lipids into the cornea begins at the superior and inferior aspects, and progresses to encircle the entire peripheral cornea. The interior border of AS has a diffuse appearance, while the exterior border is well demarcated. The clear space between the exterior border and the limbus is called the interval of vogt.Bilateral AS is a benign finding in the elderly, but it can be associated with hyperlipidemia in patients less than 50 years old. Bilateral AS may also be caused by increased levels of free fatty acids in the circulation secondary to alcohol use.Unilateral AS can be associated with contralateral carotid artery stenosis or decreased intraocular pressure in the affected eye. As these are serious medical conditions, unilateral AS should be examined by a physician.