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The exact chromosomal defect in Philadelphia chromosome is translocation. Parts of two chromosomes, 9 and 22, swap places. The result is that part of the bcr ("breakpoint cluster region") gene from chromosome 22 (region q11) is fused with part of the abl gene on chromosome 9 (region q34). Abl stands for "Abelson", the name of a leukemia virus which carries a similar protein.
The result of the translocation is a protein of p210 or sometimes p185 weight (p is a weight fraction of cellular proteins in kDa). Because abl carries a domain that can add phosphate groups to tyrosine residues ( tyrosine kinase) the bcr-abl fusion gene is also a tyrosine kinase. (Although the bcr region is also a serine/threonine kinase, the tyrosine kinase function is very relevant for therapy, as will be shown.)
The fused bcr-abl protein interacts with the interleukin 3beta(c) receptor subunit. The bcr-abl transcript is continuously active, i.e. it does not require activation by other cellular messenging proteins. In turn, bcr-abl activates a number of cell cycle-controlling proteins and enzymes, speeding up cell division. Moreover, it inhibits DNA repair, causing genomic instability and potentially causing the feared blast crisis in CML.
Philadelphia chromosome is designated Ph (or Ph') chromosome and the translocation is termed t(9;22)(q34;q11).
In the late 1990sCenturies: 19th century 20th century 21st century Decades: 1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s 2020s 2030s 2040s Years: Events and trends Computers, technology Explosive growth of the Internet; decrease in the cost of computers and other techn, Dr Brian J. Druker identified the compound then known as STI-571 as having an inhibitory effect on bcr-abl. Although it did not eradicate CML cells, it did greatly limit the growth of the tumor clone and decreased the risk of the feared "blast crisis". It was marketed in 20012001 is a common year starting on Monday (see link for calendar), and also: The International Year of the Volunteer The United Nations Year of Dialogue Among Civilizations Events January January 1 A black monolith measuring approximately nine feet tall ap by the pharmaceutical companyA pharmaceutical company is a company that discovers, markets and distributes medication. Most large companies were founded in the 20th century, and derive their market share from a few well-marketing preparations. Examples are simvastatin (ZocorŪ), which NovartisNovartis a biotechnology corporation and pharmaceutical company, had its origins in the merger of the CIBA-Geigy and Sandoz Laboratories in Basel, Switzerland. In 1998, the company made headlines with its biotechnology licensing agreement with the UC Berk as imatinib mesylateImatinib is a new drug used to treat certain types of cancer. It is a kind of chemotherapy used in treating chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies. It is occasionally referred to as C (GleevecŪ in the US, GlivecŪ in Europe).