Chronic myelogenous leukaemia (CML) is a cancer of the white blood cells. In the EU about 9600 new patients per year are diagnosed and CML accounts for 70 % of all childhood leukaemia cases. CML can currently not be cured, but kept under control with specific enzyme inhibitors. Regular monitoring of the CML patient is needed to ensure optimal treatment of the patient.
For the monitoring the number of specific genetic fragments, the BCR-ABL1 transcripts, is measured. Until now, the calibration of that monitoring method has been differently performed in various laboratories which caused non-comparable results. Therefore, a certified reference material (CRM) has been developed making use of specifically tailored plasmids suitable for the calibration of BCR-ABL1 measurements. The standardisation of the quantification of the copy numbers of BCR-ABL1 and the control gene transcripts will improve the treatment of the patient. In essence, this new CRM is an essential tool to correctly assess the human response to leukaemia treatment and to detect a relapse of individual patient early.
The CRM is a plasmid containing selected desoxyribonucleic acid (DNA) fragments specific for the transcript of breakpoint cluster region gene (BCR), the transcript of the glucuronidase beta gene (GUSB) and the fusion transcript from the BCR gene and the c-abl oncogene 1 (BCR-ABL b3a2). The CRM, coded as ERM®-AD623a–f, has been certified for the copy number ratio of these specific fragments per plasmid and for the copy number concentration of the plasmid per volume of solution. ERM-AD623 was prepared according to ISO Guide 34 and characterised by expert laboratories of demonstrated competence using the most advanced counting method for small DNA amounts, the so-called digital polymerase chain reaction. Uncertainties of the certified values were calculated in compliance with the Guide to the Expression of Uncertainty in Measurement (GUM).
The preparation and certification of ERM®-AD623 is described in detail in the corresponding certification report.