Minimal Residual Disease and Cytogenetics

Based on the current European MCL Research Network and a recent European concerted action, several European groups highly experienced in molecular cytogenetics of lymphomas and molecular genetic detection of MRD have joined. Each group runs a national reference laboratory for the European MCL Network and other lymphoma trials.

Molecular cytogenetics groups


All three groups have extensive experiences in the conventional chromosome analyses in malignant lymphomas and are national reference laboratories for the cytogenetic analysis and interphase cytogenetic methods of lymphomas applying both commercially available as well as self-developed probes.
A special focus of the groups in Kiel and Lyon is the combination of fluorescence immunophenotyping and FISH. This so called FICTION technique has been applied to detect chromosomal changes in Hodgkin’s and other lymphomas, in persistent polyclonal B-cell lymphocytosis or in the CD34 positive stem cell compartment. FICTION enables studying genetic changes in immunophenotypically defined cell populations and, thus, can significantly enhance the sensitivity of FISH. Very recently, the conventional FICTION approach has been methodologically modified allowing the simultaneous detection of up to five chromosomal loci along with a cellular antigen on a single cell level.

Molecular MRD Groups


All participating laboratories are national reference labs for PCR diagnostics and are very experienced in qualitative and quantitative PCR methods for the molecular characterization of leukemias and lymphomas.
During a previous European collaborative a very intense cooperation has been established. Aim of that European collaborative project with 32 participating labs under guidance of JJ van Dongen was the development of standardized PCR protocols for the detection of immunoglobulin (Ig) and T-cell receptor (TCR) genes and frequent chromosome aberrations, such as t(11;14), and t(14;18).
From this initial collaboration the research activity on the European level has been extended to MRD detection in ALL patients. All 4 labs are meanwhile coordinating MRD investigations within study protocols for the treatment of different lymphatic and have developed quantitative PCR methods (Real-Time-PCR) for standardized MRD quantification in the setting of prospective clinical trials.

Objectives
The major aims of this workpackage are: