Cancer Research - Europa

Keywords | Mantle cell lymphoma | therapy | molecular risk factors | minimal residual disease (MRD) |
pharmacogenomics | RNA array profi ling | proteomics |
European MCL Network
European Mantle Cell Lymphoma
Network: Translation evaluation
of molecular prognostic factors and
pharmacogenomics in European
interdisciplinary collaboration
Summary
Mantle cell lymphoma (MCL) is a subtype of malignant lymphoma
with an especially poor prognosis. Recently, a European
MCL Network of clinicians, basic scientists and pathologists
has been established to investigate the clinical as well as
molecular aspects of MCL. In previous clinical trials, the superiority
of innovative treatment options (high dose therapy,
combined immuno-chemotherapy) has been confi rmed, and
cell proliferation has been identifi ed as the most important
prognostic factor. Based on these extensive prerequisites, we
have initiated a translational approach to evaluate innovative
treatment options (like immuno-chemotherapy, radioimmunotherapy,
high dose consolidation and molecularly targeted
approaches) and molecular prognostic markers in prospective
randomised studies. All study cases are subjects of
innovative molecular analyses and continuous detection of
minimal residual disease. This translational approach will not
only lead to more eff ective therapeutic strategies based on
the molecular profi ling but also pave the way to molecular
targeted treatments.
Problem
Mantle cell lymphoma (MCL) is a distinct, clinically very
aggressive subentity of malignant lymphoma with a median
survival of three years. However, a small subset of patients
represents long-term survivors. So far, the discriminative
power of diff erent prognostic parameters has been limited
and did not allow the reliable identifi cation of the individual
patient’s risk profi le. Thus, a better understanding of the
underlying molecular mechanisms is eagerly warranted.
Aim
Based on the previously established European MCL Network
of clinicians, basic scientists and pathologists and the recent
development of innovative molecular techniques (matrix CGH,
RNA array chips, RQPCR, proteomics), we are performing
TREATMENT
a global approach to investigate innovative treatment options
of MCL and evaluate new predictive (pharmacogenomics,
minimal residual disease) and prognostic molecular markers
(genomic alterations, RNA/proteome profi les) in controlled
prospective studies. This translational approach of the European
MCL Network will not only lead to more individualised
therapeutic strategies based on the molecular risk profi le but
will also fi nally elucidate the way to future molecular targeted
treatment options in a subtype of malignant lymphoma with
an otherwise dismal clinical outcome.
Expected results
• Prospective evaluation of combined immunochemotherapy
and myeloablative consolidation in patients 65 years: R-CHOP vs. R-FC followed by IFN vs. Rituximab
maintenance.
• Regular histomorphological panel review of study cases
(subtyping according to cytological criteria).
• Prospective evaluation of a panel of proliferation-associated
and new oncogenic markers (immuno-histochemistry).
• Prospective evaluation of MRD detection (PCR, FACS,
FISH) in the patient cohort of the European MCL Network.
• Prospective evaluation of the proliferation-associated
gene signature in the patient cohort of the European
MCL Network (RNA array).
Potential applications
Malignant lymphoma is currently the fourth most frequent
malignant disease and displays the highest increase in annual
incidence of all hematological neoplasias. In this regard, the
exploration of innovative treatment strategies and evaluation
of prognostic markers in the rather rare disease of
mantle cell lymphoma is also a model disease for much
more frequent diseases which have a profound impact on
the public health system as well as the general society. The
prospective studies of the European MCL Network studies
will enable us to gain a deeper understanding of the pathophysiological
network of cell programme regulation in
malignant lymphoma. In addition, applying this multivariate
procedure, the critical biological players of malignant transformation
will be identifi ed which may represent the suitable
target genes of future treatment strategies in a disease with
otherwise dismal prognosis. Moreover, this collaboration of
outstanding clinical as well as molecular scientists will be
a paradigm for other fi elds of biological research interlinking
clinical and basic science as well as scientifi c excellence
from all over Europe.
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