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
- Institute of Human Genetics, University Hospital Kiel, Germany (R. Siebert)
- Laboratory of Cancer Genetics, University of Pamplona (J.A. Martinez-Climent)
- Unité d'Hématologie Cellulaire, Centre Hospitalier Lyon Sud (E. Callet-Bauchu)
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
- 2. Dept. of Medicine, University Hospital Kiel, Germany (C. Pott)
- Hematology Department, Rigshospitalet, Copenhagen, Denmark (N. Andersen)
- Laboratoire d'Hematologie Tour Pasteur, Paris, France (E. Macintyre)
- Dept of Immunology; Erasmus University Rotterdam, Netherlands (JJ van Dongen)
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:
- to identify diagnostically and prognostically important chromosomal changes in bone marrow and peripheral blood samples of from patients with MCL studied within the European MCL Network by means of a baseline (molecular) cytogenetic analysis,
- to optimize and comparably evaluate molecular genetic, molecular cytogenetic and phenotyping techniques for the detection of MRD,
- to investigate the prognostic importance of molecular contamination of PBCS grafts, treatment response and MRD in patients treated within the European MCL Network