prospective study for the assessment of gene dysregulation in B-cell oncogenesis using complementary DNA microarray

B-cell lymphoma displays striking heterogeneity at the clinical, genetic arid molecular levels. Clinical prognostic models can define a population at high risk for relapse following 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-CD2O 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 contribute to pathogenesis include translocations of BCL6, BCL2 and MHC class II mutations. Our study showed over expression of some genes e.g. BCL2, interleukin I, interferon receptor and low expression of MHC class H, p53, Fas and casp8-FADD. Our increasing molecular understanding of the heterogeneous subsets within B cell lymphoma will likely improve the current empiric therapy by identifying rational therapeutic targets in specific disease subtypes

Frequency of Fc gamma receptor IIIa-158V polymorphisms in Egyptian children with immune thrombocytopenic purpura

Immune thrombocytopenic purpura [ITP] is a bleeding disorder of infants, children and adults. The majority of affected children have the acute form of ITP, defined by duration of thrombocytopenia [<150 x 10[9]/L] of <6 months. Previous studies have shown that Fc gamma receptor [FcyRs] play crucial roles in platelet phagocytosis; antibodies bound to platelets have their Fc portion exposed which allows binding to monocytes/macrophages that express Fc receptors for lgG [FcgammaRs]. The Fc gammaRIIla Valine [V] has increased affinity for three separate lgG subclasses when compared with the FcgammaRIlIa Phenylalanine [F]. The aim of the present study was to assess the frequency of occurrence of the high affinity allelic variant FcgammaRllIa-158V in Egyptian children with ITP in comparison to normal individuals. Determination of FcgammaRlIIa genotype was performed for 30 ITP patients and 10 healthy control subjects by nested PCR followed by RFLP analysis. In our study, the allelic frequency of FcgammaRIlIa-158V was [76.6%] among ITP patient group in contrast to [20%] among the control group. These results suggest that FcgammaRllIa-158 V/F polymorphism contributes to the pathogenesis of childhood ITP by increased clearance of antibodysensitized platelets by the high affinity FcgammaRlIIa-158V allelic variant. Besides the epidemiologic and pathophysiologic interest, this knowl edge may be of use in the future designing of novel therapeutic interventions