1. BCR-ABL t(9;22)
Chronic Myeloid Leukaemia (CML) accounts for 15-20% of adult leukaemias. CML is a clonal haematopoietic stem cell malignancy that results in the formation of a BCR-ABL cytoplasmic fusion oncoprotein as the result of the reciprocal translocation between the long arms of chromosome 9 and chromosome 22 t(9;22) The disease is characterized by excess proliferation of myeloid progenitors that retain the capacity for differentiation during the stable or chronic phase of the disease. In addition the BCR-ABL fusion is also seen in ALL albeit more rarely. In this disease the BCR-ABL fusion is the result of a slightly different break point and results in the p190 BCR-ABL fusion protein.
A quantitative PCR (Q-PCR) utilizing the Applied Biosytems 7900 Taqman platform is used for the highly sensitive quantitative detection of BCR-ABL fusion transcripts (p210 and p230) in order to monitor disease progression and residual disease. The procedure used at KCH is harmonized to the Europe Against Cancer (EAC) guidelines to ensure that we provide highly accurate and comparable BCR-ABL / ABL transcript ratios. In addition we are one of a small group of laboratories in the UK currently engaged with the regional genetics laboratory to obtain an international conversion factor. This will enable our results can be directly compared with those of any other participating laboratory across the world. This provides even greater consistency which is desirable particularly in multi center drug trails. Our conversion factor exercise will be completed in early 2010. A separate Q-PCR assay is used to detect the p190 variant.
Persistent Q-PCR positivity after treatment is indicative of possible drug resistance and predictive of clinical relapse. A molecularly negative result is associated with disease free survival. Patients who convert to Q-PCR positivity after a negative result are at high risk of relapse. These patients may be candidates for 2nd and 3rd generation tyrosine kinase inhibitors. Failure to respond optimally to Imatinib can be caused by mutation in the p-loop domain of the translocated ABL kinase gene. Our repertoire of tests within the LMH also includes Abl kinase p-loop mutation screening which can be carried out on samples previously sent to the laboratory for BCR-ABL monitoring by request
Clinical details
Factors affecting results or interpretation: Translocation assays are performed from RNA which is very susceptible to degradation. Fresh samples give the best results and are more likely to pass our quality control.
Testing site
Synnovis : Genomics : King's College Hospital
Laboratory
SE-HMDS Laboratory for Molecular Haemato-Oncology
Sample type and volume required
1-5 ml Bone marrow and/or 20ml peripheral blood in EDTA (purple top) tube.
Presence of heparin anticoagulant will inhibit PCR applications. Clotted samples are unsuitable for DNA analysis.
Samples must be clearly labelled with the patient's first name, surname, D.O.B, hospital number and the date the sample was taken.
Storage and transport
To be sent within 2 days and stored at room temperature.
First class postage is adequate but samples must be shipped with packaging appropriate for UN 3373 samples following packing instruction 650. See link below for further details.
http://www.dft.gov.uk
Samples should be addressed to:
Central Specimen Reception,
Ground Floor, Bessemer Wing,
King's College Hospital,
Denmark Hill,
London SE5 9RS,
United Kingdom
Turnaround time
3 - 5 working days
(FIP1L1-PDGFRA assays may take up to 1 month.)
Cost
Please contact Business Development for pricing enquiries
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