Test Synonym:

BCR-ABL t(9;22) quantitative; Philadelphia Chromosome

Associations:

p210 protein in chronic myeloid leukemia

Test Synonym:

83891 – Molecular isolation
83892 – Enzymatic digestion
83902 – Reverse transcriptase
83894 – Separation by gel electrophoresis
83896 X2 – Nucleic acid probe
83898 X2– Amplification of patient nucleic acid, primer pair

83912-26 – Interpretation and report

Turnaround Time:

3-5 days; specimens accepted Monday through 1:00PM on Friday. Assay run once/week

Methodology:

Quantitative reverse transcriptase Polymerase Chain Reaction (qPCR)

Specimen Requirements:

Technical Bulletin qPCR

10.0ml (min. 9.0ml) peripheral blood in EDTA

5.0ml (min. 2.5ml) bone marrow in EDTA

Causes for Rejection:

Specimen >48 hrs. old

Specimen clotted

Specimen stored or shipped at incorrect temperature

Specimen in incorrect anticoagulant

Insufficient specimen volume

Specimen Stability:

Specimen must be received by MPLN within 48 hrs. of collection

Stable at 2-8°C

Storage and Handling:

Ship peripheral blood and bone marrow at ambient temperature (do not ship on ice or cold pack; do not ship to arrive after 1:00PM on Friday, or on weekends)

Reference Range:

Positive: major BCR-ABL fusion quantified relative to ABL and to prior test result
Negative: major BCR-ABL fusion not detected (<0.001% BCR-ABL/ABL)

Indication:

The Philadelphia chromosome results from a translocation [t(9;22)(q34;q11.2)] that fuses the c-Abl proto-oncogene on chromosome 9 to the BCR (breakpoint cluster region) gene on chromosome 22¹. Philadelphia chromosome t(9;22) is found in 95% chronic myeloid leukemias (CML) based on conventional cytogenetics (karyotype) and >99% CML patients based on FISH analysis. 20% of adult acute lymphoblastic leukemia (ALL), ~5% of pediatric ALL and ~2% of acute myeloid leukemia (AML) are also Philadelphia chromosome positive. There are two main classes of translocation seen in Ph+ cells: major and minor. The major class accounts for 99% of all CML patients and 50-70% of adult ALL. The Bcr-Abl protein exhibits enhanced tyrosine kinase activity. Inhibition of this enzymatic activity by Gleevec® is effective in the treatment of CML². The primary clinical utilities for the StrataFLEX BCR-ABL major quantitative PCR test  include (a) the determination of a baseline level of BCR-ABL expression in newly diagnosed CML patients, and (b) the monitoring of patients for molecular evidence of minimal residual disease (MRD) or molecular remission in response to conventional chemotherapy or allogeneic stem cell transplantation³. Molecular monitoring of BCR-ABL expression should be repeated at a minimum of three-month intervals to establish the kinetics (trend) of BCR-ABL expression³.

References:

1. Kurzrock et al. (2003). Philadelphia chromosome-positive leukemias: from basic mechanisms to molecular therapeutics. Ann Intern Med 138:819
2. Hughes et al. (2003). Frequency of major molecular responses to Imatinib or Interferon Alfa plus Cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med 349(15):1423
3. Olavarria. et al. (2001). Early detection of BCR-ABL transcripts by quantitative reverse transcriptase–polymerase chain reaction predicts outcome after allogeneic stem cell transplantation for chronic myeloid leukemia. Blood 97:1560