Synapse BCR-ABL quantitative assay is an automated and highly accurate clinical diagnostic tool for monitoring patients with minimal residual disease of chronic myelogenous leukemia and for low and high throughput oncology research labs.  The standardized genomic application provides for more accurate diagnosis, initiation of targeted drug therapy and also for post-therapy follow-up for the presence of minimal residual disease.
 

The system is based on automated sample preparation with reverse transcriptase-polymerase chain reaction-based fluorescent signal detection. The BCR-ABL nested real-time PCR assay provides rapid, standardized test reporting in about 2 hours. A hematologist provides a clinical interpretation of the test.
 

Ordering Information  

Test Name: BCR-ABL Assay

Test Description: BCR-ABL Quantitative real-time reverse transcription-PCR (qRT-PCR) Assay.

Specimen Type: 8 mL Whole Blood EDTA.

Specimen Requirements: Ambient. Ship immediately by overnight courier.

Assay Reporting Time: Maximum two days from receipt of specimen. 
 

Test Information

Patients with chronic myeloid leukemia (CML) invariably harbor a chromosomal translocation that corresponds to fusion of the BCR and ABL genes at the DNA level. The translated fusion product is an oncogenic protein with increased ABL tyrosine kinase activity causing neoplastic transformation.
 

Classic cytogenetics (chromosome G-banding) is still considered essential to establish a new diagnosis of CML. Utility of chromosome banding for monitoring minimal residual disease is limited by the need for satisfactory cell culture for visualization of the metaphases.4 Furthermore, the relatively low number of cells examined results in sensitivities similar to those of the routine histological examination of the bone marrow for the presence of leukemic cells.5 Practically the sensitivity can be increased marginally using fluorescence in situ hybridization and examining more white blood cells (WBCs).
 

To date, however reverse transcription-polymerase chain reaction (RT-PCR) is considered the most sensitive technique available for detecting low copy numbers of the BCR-ABL gene fusion with reported sensitivities varying from one leukemia cell out of 105 to 106 normal white blood cells.
 

Pharmacogenomic application

Discovery of this molecular mechanism has resulted in the advent of targeted drug therapies which are indicated for the treatment of newly diagnosed adult patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. The Ph chromosome produces the abnormal protein, called the Bcr-Abl protein. 
Targeted treatment is also indicated for the treatment of patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in blast crisis, accelerated phase, or in chronic phase after failure of alternate therapies.
 

Monitoring of minimal residual disease in CML

Monitoring of minimal residual disease in CML using RT-PCR-based molecular techniques confers the ability to assess initial response in patients undergoing drug therapy or after bone marrow transplantation. It also can alert physicians of potential relapses even in cases with complete cytogenetic remission. This information is invaluable to adjust treatment plans and bears important prognostic significance. Moreover, it has recently been established that the degree of molecular response at the time of or after achieving complete cytogenetic remission is an independent prognostic factor for progression-free survival.
 

References

1. Nashed AL, Rao KW, Gulley ML. Clinical applications of BCR-ABL molecular testing in acute leukemia. J Mol Diagn. 2003;5:63–72.
2. Gutterman JU, Mavligit G, Burgess MA, McCredie KB, Hunter C, Freireich EJ, Hersh EM. Immunodiagnosis of acute leukemia: detection of residual disease. J Natl Cancer Inst. 1974;53:389–392. 
3. Pelz AF, Kroning H, Franke A, Wieacker P, Stumm M. High reliability and sensitivity of the BCR/ABL1 D-FISH test for the detection of BCR/ABL rearrangements. Ann Hematol. 2002;81:147–153. 
4. Goldman J. Monitoring minimal residual disease in BCR-ABL-positive chronic myeloid leukemia in the imatinib era. Curr Opin Hematol. 2005;12:33–39.
5. Zsolt Jobbagy, Reuel van Atta,†Kathleen M. Murphy, James R. Eshleman, Christopher D. Gocke. Evaluation of the Cepheid GeneXpert BCR-ABL Assay. Journal of Molecular Diagnostics, Vol. 9, No. 2, April 2007.
6 Press RD, Love Z, Tronnes AA, Yang R, Tran T, Mongoue-Tchokote S, Mori M, Mauro MJ, Deininger MW, Druker BJ. BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate-treated patients with CML. Blood. 2006;107:4250–4256.