Genomic & Molecular Pathology

Quantitative Analysis for BCR-ABL Fusion Transcripts

The Philadelphia chromosome (Ph) resulting from the reciprocal translocation of chromosomes 9 and 22 [t(9:22)(q34;q11)] gave rise to a fusion BCR-ABL gene. Philadelphia chromosome was found in about 90 to 95 percent of chronic myeloid leukemia (CML) cases. This translocation also has been found in 25 to 30 percent of adult and in 2 to 5 percent of pediatric acute lymphoblastic leukemia (ALL) cases. In the vast majority of the patients, the breakpoints in the BCR gene are clustered within three well-defined regions: 1) a 55kb sequence of the first intron, called the minor breakpoint cluster region (m-bcr); 2) a 5.8kb region spanning exons 12-16, called the major breakpoint cluster region (M-bcr); and 3) intron 19 called micro-bcr (µ-bcr). Micro-bcr is an extremely rare event. The M-bcr mainly has two products: b2a2 and b3a2. e1-a2 is the main product of m-bcr. This analysis is to quantify the relative amount of the above fusion transcripts using real-time PCR. Fusion transcripts can be detected at the dilution of 1 to 1,000,000 in this laboratory using RNA from M-bcr positive cell line. However, the test sensitivity could be affected by sample collection and processing. Usually relative copy number of fusion transcripts between 1/1000 and 1/10,000 can be reliably detected. Using the ABL gene as an internal control, we calculate the normalized copy number (NCN) of BCR-ABL as well as the log reduction. Because of the variability during specimen collection and laboratory processing, only changes of 0.5 log or greater should be considered to be significant.

Indications for Testing

Diagnosis of chronic myeloid leukemia (CML)
Identify acute lymphoblastic leukemia (ALL) with t[9;22] BCR-ABL translocation
Assess prognosis in patients with ALL
Monitor the effectiveness of therapy
Monitor minimal residual disease (MRD)

Sample Requirements

Infants: 2 – 3 mL whole blood (or bone marrow) in purple top EDTA tube
Children (>2 years) and adults: 3-4 mL whole blood (or bone marrow) in purple top EDTA tube

Sample Handling

Blood samples stored overnight should be refrigerated or kept cold. Blood samples should never be frozen. Specimens being sent from outside facilities should be packaged with a cold pack according to standard medical safety practices. The specimen should be shipped by overnight priority (scheduled to arrive by Friday morning at the latest).

Shipping Address

Center for Human Genetics Laboratory
10524 Euclid Ave, Sixth Floor
Cleveland, OH 44106
216-983-1134

For local samples, please call Client Service (216-844-5227) to arrange for sample pick-up.

Turnaround Time

One week

CPT Codes

81206, 81207

Please submit a completed Hematology/Oncology Specimens requisition (PDF) for each sample.