Diffuse large B cell lymphomas

Intrinsic resistance of lymphoma cells to apoptosis is a probable mechanism causing chemotherapy resistance and eventual fatal outcome in patients with diffuse large B cell lymphomas (DLBCL). We investigated whether microarray expression profiling of apoptosis related genes predicts clinical outcome in 46 patients with primary nodal DLBCL. Unsupervised cluster analysis using genes involved in apoptosis (N=246) resulted in 3 separate DLBCL groups partly overlapping with GCB versus ABC like phenotype. One group with poor clinical outcome was characterized by high expression levels of pro-and anti-apoptotic genes involved in the intrinsic apoptosis pathway. A 2nd group, also with poor clinical outcome, was characterized by high levels of apoptosis inducing cytotoxic effector genes, possibly reflecting a cellular cytotoxic immune response. The 3rd group showing a favourable outcome was characterized by low expression levels of genes characteristic for both other groups. Our results suggest that chemotherapy refractory DLBCL are characterized either by an intense cellular cytotoxic immune response or by constitutive activation of the intrinsic mediated apoptosis pathway with concomitant downstream inhibition of this apoptosis pathway. Consequently, strategies neutralizing the function of apoptosis-inhibiting proteins might be effective as alternative treatment modality in part of chemotherapy refractory DLBCL. Keywords: expression profiling B lymphomas As an internal control for unsupervised clustering duplicate experiments were performed for 5 lymphoma samples (indicated as a and b, respectively), including isolation of mRNA from separate tissue samples at different days. Two tonsils with reactive follicular hyperplasia were included to compare the DLBCL with normal hyperplastic lymphoid tissue.