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The Philadelphia chromosome or Philadelphia translocation is a specific abnormality of chromosome 22, which is unusually short, as an acquired abnormality that is most commonly associated with chronic myelogenous leukemia (CML).〔 It is the result of a reciprocal translocation between chromosome 9 and chromosome 22, which is specifically designated t(9;22)(q34;q11). This gives rise to a fusion gene, bcr-abl, that juxtaposes the ''Abl1'' gene on chromosome 9 (region q34) to a part of the ''BCR'' ("breakpoint cluster region") gene on chromosome 22 (region q11). The presence of this translocation is a highly sensitive test for CML, since 95% of people with CML have this abnormality (the remainder have either a cryptic translocation that is invisible on G-banded chromosome preparations, or a variant translocation involving another chromosome or chromosomes as well as the long arm of chromosomes 9 and 22). However, the presence of the Philadelphia (Ph) chromosome is not sufficiently specific to diagnose CML, since it is also found in acute lymphoblastic leukemia (ALL, 25–30% in adult and 2–10% in pediatric cases) and occasionally in acute myelogenous leukemia (AML). ==Molecular biology== The chromosomal defect in the Philadelphia chromosome is a translocation, in which parts of two chromosomes, 9 and 22, swap places. The result is that a fusion gene is created by juxtapositioning the ''Abl1'' gene on chromosome 9 (region q34) to a part of the ''BCR'' ("breakpoint cluster region") gene on chromosome 22 (region q11). This is a reciprocal translocation, creating an elongated chromosome 9 (termed a derivative chromosome, or ''der 9''), and a truncated chromosome 22 (''the Philadelphia chromosome).'' In agreement with the International System for Human Cytogenetic Nomenclature (ISCN), this chromosomal translocation is designated as t(9;22)(q34;q11). ''Abl'' stands for "Abelson", the name of a leukemia virus which carries a similar protein. Translocation results in an oncogenic BCR-ABL gene fusion that can be found on the shorter derivative 22 chromosome. This gene encodes for a Bcr-abl fusion protein. Depending on the precise location of fusion, the molecular weight of this protein can range from 185 to 210 kDa. Consequently, bcr-abl is referred to as p210 or p185. Three clinically important variants are the p190, p210, and p230 isoforms. p190 is generally associated with acute lymphoblastic leukemia (ALL), while p210 is generally associated with chronic myeloid leukemia but can also be associated with ALL. p230 is usually associated with chronic neutrophilic leukemia.〔 Additionally, the p190 isoform can also be expressed as a splice variant of p210. The Abl gene expresses a membrane-associated protein, a tyrosine kinase, and the BCR-Abl transcript is also translated into a tyrosine kinase. The activity of tyrosine kinases is typically controlled by other molecules, but the mutant tyrosine kinase of the BCR-Abl transcript codes for a protein that is "always on" or continuously activated, which results in unregulated cell division (i.e. cancer). Although the BCR region also expresses serine/threonine kinases, the tyrosine kinase function is very relevant for drug therapy. Tyrosine kinase inhibitors (such as imatinib and sunitinib) are important drugs against a variety of cancers including CML, renal cell carcinoma (RCC) and gastrointestinal stromal tumors (GISTs). The fused ''BCR-Abl'' protein interacts with the interleukin-3 receptor beta(c) subunit. The ABL tyrosine kinase activity of ''BCR-Abl'' is elevated relative to wild-type ABL. Since ABL activates a number of cell cycle-controlling proteins and enzymes, the result of the ''BCR-Abl'' fusion is to speed up cell division. Moreover, it inhibits DNA repair, causing genomic instability and potentially causing the feared blast crisis in CML. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Philadelphia chromosome」の詳細全文を読む スポンサード リンク
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