A Prospective Study for the Assessment of Gene Dysregulation in B-Cell Oncogenesis Using Complementary DNA Microarray,AZZA ABOUL ENEIN, WAFAA EL-METNAWY, FAROUK HAGGAG, NEIRMINE A. EL-DESSOKI, DOAA M. SOLIMAN, REHAM AFIFI and IMAN ABDEL MOHSEN
Abstract
B-cell lymphoma displays striking heterogeneity at the clinical, genetic and molecular levels. Clinical prognostic models can define a population at high risk for relapse fol-lowing empiric chemotherapy, although such models do not account for underlying biologic differences among tumors. Despite recent advances in empiric chemotherapy, including interval reduction of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and the incorporation of anti-CD20 monoclonal antibodies, a significant proportion of patients still die of their disease. Gene expression profiling has shed light on the molecular heterogeneity within B cell lymphoma by highlighting similarities between subsets of tumors and normal B cells, identifying features associated with unfavorable responses to empiric combination chemotherapy and defining robust subtypes with comprehensive transcriptional signatures. Commonly observed genetic abnormalities that likely contrib-ute to pathogenesis include translocations of BCL6, BCL2 and MHC class II mutations. Our study showed over expression of some genes e.g. BCL2, interleukin 1, interferon receptor and low expression of MHC class II, p53, Fas and casp8- FADD. Our increasing molecular understanding of the heter-ogeneous subsets within B cell lymphoma will likely improve the current empiric therapy by identifying rational therapeutic targets in specific disease subtypes.