Measurable (minimal)
residual disease (MRD)

The molecular genetic determination of MRD is based on the detection of leukemia-specific DNA sequence variants, chromosomal translocations and genomic rearrangements. Using molecular biology testing methods, patient-specific mutations can be identified at diagnosis and followed during the course of disease and treatment.

The molecular genetic detection of MRD is based on the functional principle of the polymerase chain reaction (PCR). This is an enzyme-based method for the specific amplification of nucleic acid sequences. Analytical methods used in routine molecular genetic MRD diagnostics include: Next-generation Sequencing (NGS) using ultra-deep amplicon sequencing, digital PCR (dPCR), quantitative real-time PCR (qPCR), and fragment length analysis.

An example of this is shown by patients with chronic myeloid leukemia (CML), where molecular genetic MRD diagnostics play a central role in guiding therapy. More than 95% of all CML patients have a reciprocal chromosome translocation at diagnosis, which leads to a BCR-ABL1 fusion gene. Quantification of the BCR-ABL1 fusion transcript by sequence-specific qPCR is suitable for highly sensitive determination of MRD burden. An increase in the mutational load of the BCR-ABL1 fusion transcript in CML patients in complete molecular remission may indicate treatment failure.

Other mutations for MRD assessment based on current diagnostic guidelines (Schuurhuis et al., 2018, Döhner et al., 2017) and routinely detected in acute leukemias are as follows:

For a complete list of all markers we offer, please refer to the additional section Molecular Genetics of the request form.

Leukemia-associated aberrant immunophenotypes (LAIPs) that do not – or very rarely – occur in this constellation on the cells of normal bone marrow can be detected in cases of acute leukemia. They are divided into:

Of central importance is the correct identification of an LAIP, so precise knowledge of – and benchmarking with – the immunophenotype in the normal bone marrow is essential for MRD quantification. The LAIP is often characterized by the expression intensity of a particular antigen, which can vary significantly from case to case. It is therefore necessary to define one or several LAIPs for each patient individually. Hence, individual identification of the LAIP at the time of diagnosis is a precondition to enable MRD testing. The use of an extensive panel of antibodies is necessary for detection of an LAIP, especially for AML, in order to identify rare LAIPs and to make them available for downstream progress examinations.