December 14, 2017
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Home >> Newsletter >> Philadelphia Chromosome عربي

Leukaemia

Philadelphia Chromosome by RQ-PCR

 

The lpsogen Fusion Quanttm M-bcr and m-bcr Kits are unique molecular kits providing standardization and accurate quantification of fusion gene transcripts in leukaemia.

 

Introduction

 

The BCR-ABL fusion gene is associated with formation of the Philadelphia chromosome (Ph) and is one of the most common genetic abnormalities detected in leukaemias. In Acute Lymphoblastic Leukaemia (ALL), Ph is detected in 25-30% of adult and 2-5% of childhood cases. Less frequently, it is associated with Acute Myeloid Leukaemia. In the ALL subset, this genetic lesion is known to confer a very poor prognosis, and consequently, its detection is important in planning aggressive therapies, including allogenic bone marrow transplant. In addition, the Ph chromosome is found in more than 95% of Chronic Myeloid Leukaemia (CML) cases and is the hallmark of this disease. At the molecular level, the Ph chromosome or t (9:22) results in the juxtaposition of the 5' part of the BCR gene (chromosome 22) to the 3' part of the ABL gene (chromosome 9). In the vast majority of patients, the breakpoints in the BCR gene are clustered within three well defined regions (i) a 55 Kb sequence of the first intron, called the minor breakpoint cluster region (m-bcr), (ii) a 5.8 Kb region spanning exons 12 to 16, called the major breakpoint cluster region (M-bcr), and (iii) finally intron 19, called μ-bcr (very rare). In the case of m-bcr breakpoints, the first exon of the BCR gene (e1) is juxtaposed to the second exon of the ABL gene (a2). The resultant fusion transcript (e1-a2) encodes a 190 KDa chimeric protein (p190). This type of BCR -ABL fusion gene is found in 65% of adults and 80% of children with Ph positive ALL. Only in sporadic cases is the p190 encoding BCR-ABL gene found in CML.

 

The quantification of BCR -ABL transcripts is useful in monitoring minimal residual disease and genetic recurrence in patients known to harbour the translocation. By quantifying the transcript levels, successive patient samples nay be monitored for changes in copy number.

 

Two separate assays are available, one for the major breakpoint M-bcr, typically seen in CML, and one for the minor breakpoint m-bcr, typically seen in ALL.

 

*Run out time: 48 hours.

 


 
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