bcr (Breakpoint Cluster Region) Gene Rearrangement |
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The Philadelphia chromosome (Ph) can be detected in 90 to 95% of patients with chronic myelogenous leukemia (CML). Cytogenetic demonstration of the Ph chromosome is an important feature in the differential diagnosis of CML. The Ph chromosome is also present in approximately 20% of adults and 5% of children with acute lymphoblastic leukemia and 2% of adults with acute myelogenous leukemia. The presence of the Philadelphia chromosome in acute leukemia connotes a poorer prognosis.
The Ph chromosome arises from a translocation of most of the cellular abl proto-oncogene on chromosome 9 to the breakpoint cluster region (bcr) gene on chromosome 22. The resultant fused gene codes for an aberrant chimeric protein, which has increased tyrosine kinase activity. Increased levels of this enzyme adversely affect the control of normal cell growth and are probably important in the pathogenesis of Philadelphia chromosome positive acute and chronic leukemias.
Analysis of bcr gene rearrangements has several advantages over conventional cytogenetic identification of the Philadelphia chromosome; millions of cells are analyzed, dividing cells are not required, and peripheral blood can be used instead of bone marrow. Also, bcr gene rearrangements are usually positive in CML cases that are cytogenetically negative for Philadelphia chromosome. These patients have the same clinical course as patients with classical Philadelphia chromosome positive CML. Bcr gene rearrangement analysis is the only indication of malignancy when these patients enter hematologic remission and provides a critical adjunct to diagnosis and follow-up. Bcr gene rearrangement is detected by Southern Blot analysis.
Acceptable specimens include:
- Whole blood -Two 5 mL lavender top tubes, transported at room temperature.
- Bone marrow - One 5 mL tube, transported at room temperature.
- Tissue - 5 x 5 x 5 mm piece trimmed of fat and connective tissue transported on dry ice.
- Body fluids - 50 mL minimum.
Reference value is no gene rearrangement detected.
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