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Cell Biochemistry Martinsried |
G.Valet, H.G.Höffkes1)
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1. Background:
Diffuse large-B-cell lymphomas (DLBCL) represent the most frequent
lymphoma in adults. Between 35 to 40 % of patients are cured by
anthracyclin therapy. The relatively high therapeutic failure
rate may be explained by the existence of subgroups of lymphomas with
responsivenes to other chemotherapeutic agents.
- The study of gene-expression profiles permitted the characterization
of a germinal-center B-cell-like subgroup with good therapy
response and of the activated B-cell-like subgroup with poor outcome.
Recent
gene expression profiling
(L1)
using "Lymphochip" arrays (7399 gene spots) has permitted to
characterize the additional type3 large B-cell lymphoma by
an hierarchical clustering algorithm. A method was developed
to predict the likelihood of survival after chemotherapy for
diffuse large B-cell lymphoma. This predictor of prognosis and the
international prognostic index (IPI) are independent prognostic
indicators.
- The data have been reanalyzed by fuzzy neural network in combination
with the SWEEP operator method. An overall accuracy of 72%
correct decisions was obtained
(L2).
2. Goal:
Predictors of prognosis are patient group
oriented and valuable for therapeutic patient stratification.
They are, however, not informative as outcome predictors
for individual patients prior to an envisaged chemotherapy.
- The goal of a study on the above
data
is directed towards the pretherapeutic identification (>95% correct)
of high risk DLBCL patients by a
data sieving algorithm
3. Results: Present results suggest that predictive identification for individual patients are possible and that predictive (fig.1) and prognostic (fig.2) data patterns are different although a certain number of lymphocyte associated parameters are selected in both cases. Eight of the differentially expressed genes in the predictive pattern concern genes of unknown function. This seems of particular interest for further studies on gene regulation in DLBCL.
4. Conclusion: The classification of the reported data suggest that individualized pretherapeutic risk assessment for patient survival is possible (L3 ).
L1
Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI,
Gascoyne RD, Müller-Hermelink HK, Smeland EB, Staudt LM:
The use of molecular profiling to predict survival after
chemotherapy for diffuse large B-cell lymphoma.
NEJM 346:1937-47(2002)
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