Association of HLA Class I and Class II genes with bcr-abl transcripts in leukemia patients with t(9;22) (q34;q11)

BACKGROUND: Based on the site of breakpoint in t(9;22) (q34;q11), bcr-abl fusion in leukemia patients is associated with different types of transcript proteins. In this study we have seen the association of HLA genes with different types of bcr-abl transcripts. The association could predict the bcr-abl peptide presentation by particular HLA molecules. METHODS: The study included a total of 189 patients of mixed ethnicity with chronic myelogenous leukemia and acute lymphocytic leukemia who were being considered for bone marrow transplantation. Typing of bcr-abl transcripts was done by reverse transcriptase PCR method. HLA typing was performed by molecular methods. The bcr-abl and HLA association was studied by calculating the relative risks and chi-square test. RESULTS: Significant negative associations (p < 0.05) were observed with HLA-A*02 (b2a2, e1a2), -A*68 (b2a2, b3a2, e1a2), -B*14 (b2a2, b3a2, e1a2), -B*15 (b2a2, b3a2), -B*40 (b2a2), -DQB1*0303 (b2a2, b3a2), -DQB1*0603 (b2a2), -DRB1*0401 (e1a2), -DRB1*0701 (b3a2), and -DRB1*1101 (b2a2). CONCLUSIONS: The negative associations of a particular bcr-abl transcript with specific HLA alleles suggests that these alleles play a critical role in presenting peptides derived from the chimeric proteins and eliciting a successful T-cell cytotoxic response. Knowledge of differential associations between HLA phenotypes and bcr-abl fusion transcript types would help in developing better strategies for immunization with the bcr-abl peptides against t(9;22) (q34;q11)-positive leukemia

Parasite fate and involvement of infected cells in the induction of CD4+ and CD8+ T cell responses to Toxoplasma gondii

During infection with the intracellular parasite Toxoplasma gondii, the presentation of parasite-derived antigens to CD4+ and CD8+ T cells is essential for long-term resistance to this pathogen. Fundamental questions remain regarding the roles of phagocytosis and active invasion in the events that lead to the processing and presentation of parasite antigens. To understand the most proximal events in this process, an attenuated non-replicating strain of T. gondii (the cpsII strain) was combined with a cytometry-based approach to distinguish active invasion from phagocytic uptake. In vivo studies revealed that T. gondii disproportionately infected dendritic cells and macrophages, and that infected dendritic cells and macrophages displayed an activated phenotype characterized by enhanced levels of CD86 compared to cells that had phagocytosed the parasite, thus suggesting a role for these cells in priming naïve T cells. Indeed, dendritic cells were required for optimal CD4+ and CD8+ T cell responses, and the phagocytosis of heat-killed or invasion-blocked parasites was not sufficient to induce T cell responses. Rather, the selective transfer of cpsII-infected dendritic cells or macrophages (but not those that had phagocytosed the parasite) to naïve mice potently induced CD4+ and CD8+ T cell responses, and conferred protection against challenge with virulent T. gondii. Collectively, these results point toward a critical role for actively infected host cells in initiating T. gondii-specific CD4+ and CD8+ T cell responses

Breast Malignancies in Children: Presentation, Management, and Survival.

PURPOSE: Pediatric breast malignancies are rare, and descriptions in the literature are limited. The purpose of our study was to compare pediatric and adult breast malignancy. METHODS: We performed a retrospective cohort study using the National Cancer Data Base comparing patients ≤21 years to those \u3e21 years at diagnosis (1998-2012). Generalized linear models estimated differences in demographic, tumor, and treatment characteristics. Cox regression was used to compare overall survival. RESULTS: Of 1,999,181 cases of invasive breast malignancies, 477 (0.02%) occurred in patients ≤21 years. Ninety-nine percent of adult patients had invasive carcinoma compared with 64.8% of pediatric patients with the remaining patients having sarcoma, malignant phyllodes, or malignancy not otherwise specified (p \u3c 0.001). Pediatric patients were twice as likely to have an undifferentiated malignancy [relative risk (RR) 2.19; 95% confidence interval (CI) 1.72-3.79]. Half of adults presented with Stage I disease compared with only 22.7% of pediatric patients (p \u3c 0.001). Pediatric patients were 40% more likely to have positive axillary nodes (RR 1.42; 95% CI 1.10-1.84). Among patients with invasive carcinoma, pediatric patients were more than four times as likely to receive a bilateral than a unilateral mastectomy compared with adults (RR 4.56; 95% CI 3.19-6.53). There was no difference in overall survival between children and adults. CONCLUSIONS: Pediatric breast malignancies are more advanced at presentation, and there is variability in treatment practices. Adult and pediatric patients with invasive carcinoma have similar overall survival

Colorectal carcinoma in pediatric patients: A comparison with adult tumors, treatment and outcomes from the National Cancer Database.

BACKGROUND: Pediatric colorectal cancer (CRC) is rare. Comparison with adult CRC tumors, management, and outcomes may identify opportunities for improvement in pediatric CRC care. STUDY DESIGN: CRC patients in the National Cancer Data Base from 1998 to 2011, were grouped into Pediatric (≤21years), early onset adult (22-50) and older adult (\u3e50) patients. Groups were compared with χ(2) and survival analysis. RESULTS: A total of 918 pediatric (Ped), 157,779 early onset adult (EA), and 1,304,085 older adults (OA) were identified (p CONCLUSIONS: This is the largest cohort of pediatric CRC patients, revealing more aggressive tumor histology and behavior in children, particularly in rectal cancer. Despite standard oncologic treatment, age ≤21 was a significant predictor of mortality. This is likely owing to worse tumor biology rather than treatment disparities and may signal the need for different therapeutic strategies