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

Expression of the multidrug resistance protein MDR1/P-glycoprotein in acute leukemia patients

Therapeutic resistance is a major obstacle in the treatment of acute leukemia which has been closely associated with treatment failure. One of the mechanisms of drug resistance involves over expression of the multidrug resistance gene product, P glycoprotein [MDR1/pgp]. In this study the extent of MDR1/Pgp expression in patients suffering from acute leukemia and its possible prognostic role were evaluated. Twenty -five leukemia patients with mean age of 22.3 +/- 19.6 years were evaluated for percentage cells expressing MDR1/Pgp and mean fluorescence index reflecting intensity of expression using flow cytometry. Evaluation was performed at diagnosis and 21 days after induction chemotherapy to assess possible prognostic role of Pgp expression. 10 age matched control subjects were enrolled in the study. At diagnosis, mean percentage of cells expressing MDR1/Pgp were significantly higher in acute leukemia patients compared to controls [P < 0.05]. Further significant elevation of both percentage cells expressing Pgp and Mil was noted comparing patient results before and after induction chemotherapy [P < 0.05 for each]. On comparing percentage of cells expressing Pgp and MF1 in responders and non responders to standard therapy protocols, there was no significant difference before initiation of therapy, while after induction chemotherapy both parameters showed a statistically significant higher values in non-responders compared to responders [P < 0.05 for each]. Thus, increased expression of MDR1/Pgp is noted in acute leukemia cases with more evident over-expression after use of chemotherapy. Enhanced Pgp expression can affect the response of acute leukemia patients to chemotherapy opening the way for a possible role of MDR1 modulating drugs

Effect of different apheresis techniques on stem cell yield in autologous peripheral blood stem cell [PBSC] transplant patients

Peripheral blood progenitor cells [PBSC] have been extensively used to restore haematopoiesis after myeloablative chemotherapy. Large volume leukapheresis [LVL] was defined as the processing of greater than 3 volumes of blood at one setting, by which more hematopoietic progenitor cells are mobilized to the peripheral blood. The aim of this work was to study the effect the use of large and small apheresis techniques on stem cell yield in patients undergoing autologous PBSC transplantation. In this study 41 PBSC transplant patients were evaluated to assess the effect of use of small and large volume apheresis techniques on the transplantation process. The study included 17/41 cancer breast cases, 22/41 lymphoma cases and 2/41 leukemia patients. Small volume apheresis was performed in 9/41 [22%] of patients for whom 33 sessions of apheresis were performed while large volume apheresis technique was used in 32/41 [78%] of patients in 60 apheresis sessions. Comparing the outcome of these techniques showed that patients subjected to large blood volume apheresis technique showed a significantly higher mean yield when compared to small blood volume apheresis, [p<0.05]. Assessment of relation between number of mobilizations needed for the patient and chemotherapy potency revealed significant relation as heavily treated patients needed more mobilization rounds [p<0.05]. Yield of CD34 positive cells was affected by the number of mobilization rounds. Patients who needed a single round of mobilization showed a significant higher stem cell yield than with 2 rounds of mobilization [P.<0.01].Correlation study in this work revealed significant positive correlation between CD34+ cell yield [CD34+ cells x 10[6]/kg] and absolute CD34+ cell number in peripheral blood before harvest [precount] using the large volume technique with [r value = 0.87] and [p value < 0.01] while this significant correlation was not detected using small volume technique. Another significant positive correlation was found between CD34+ cell yield [CD34+ cells x 10[6]/kg] and the volume of blood processed during apheresis [r value=0.57] and [p<0.05]. Comparing the blood picture counts before and after harvesting using the large volume techniques, there was a significant difference between preharvest and postharvest mean hemoglobin and hematocrit [P <0.05 for each]. Assessment of effect of small volume on pre and postharvest blood picture counts revealed no significant difference between any of the counts before and after harvesting