Chronic myelogenous leukemia pathophysiology
|
Chronic myelogenous leukemia Microchapters |
|
Differentiating Chronic myelogenous leukemia from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Chronic myelogenous leukemia pathophysiology On the Web |
|
American Roentgen Ray Society Images of Chronic myelogenous leukemia pathophysiology |
|
Directions to Hospitals Treating Chronic myelogenous leukemia |
|
Risk calculators and risk factors for Chronic myelogenous leukemia pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2]
Overview
Genes involved in the pathogenesis of chronic myelogenous leukemia include BCR and ABL.
Pathogenesis
Genetics
In Philadelphia chromosome translocation, parts of two chromosomes (the 9th and 22nd by conventional karyotypic numbering) switch places. 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 (p is a weight measure of cellular proteins in kDa). 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 which 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.[1]
Gallery
-
![Philadelphia chromosome. A piece of chromosome 9 and a piece of chromosome 22 break off and trade places. The bcr-abl gene is formed on chromosome 22 where the piece of chromosome 9 attaches. The changed chromosome 22 is called the Philadelphia chromosome.[2]](/images/3/30/Bcr-abl.jpg)
Philadelphia chromosome. A piece of chromosome 9 and a piece of chromosome 22 break off and trade places. The bcr-abl gene is formed on chromosome 22 where the piece of chromosome 9 attaches. The changed chromosome 22 is called the Philadelphia chromosome.[2]
-
![Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell[2]](/images/d/d7/CDR526538-571.jpg)
Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell[2]
![Philadelphia chromosome. A piece of chromosome 9 and a piece of chromosome 22 break off and trade places. The bcr-abl gene is formed on chromosome 22 where the piece of chromosome 9 attaches. The changed chromosome 22 is called the Philadelphia chromosome.[2]](/index.php/File:Bcr-abl.jpg)
![Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell[2]](/index.php/File:CDR526538-571.jpg)