BCL11A Polymorphism in Egyptian Children with ß-Thalassemia: Relation to Phenotypic Heterogeneity.

Fetal hemoglobin (HbF) is a potent genetic modifier of ß-thalassemia phenotype. B-cell lymphoma 11A ( BCL11A ) gene results in significant silencing of HbF. The aim of this study was to assess the prevalence of different BCL11A genotypes among a cohort of Egyptian children with ß-thalassemia and to correlate them to HbF and clinical severity score. Eighty-two children with ß-thalassemia (aged 12.95 ± 3.63 years) were recruited from the Pediatric Hematology Clinic, Ain Shams University. They were divided based on the clinical severity of ß-thalassemia into three subgroups: 20 mild (24.4%), 24 moderate (29.3%), and 38 severe (46.3%). Age, gender, age of diagnosis, initial HbF level, transfusion history, and history of splenectomy were assessed. Anthropometric measures, signs of anemia and hemosiderosis, and the severity score were determined. Laboratory investigations such as complete blood picture, ferritin, and single gene polymorphism genotyping of the rs11886868 were also performed. Our findings showed that 16 children had CC genotype (19.5%), 38 had TC genotype (46.3%), and 28 had TT genotype (34.1%) of the rs#. ß-thalassemia children with TT genotype had significantly higher severity scoring than the other two groups ( p < 0.001). Moreover, mean initial HbF was found to be lower in children with TT genotype followed by TC and CC genotypes ( p < 0.001). Increased γ-globin expression associated with BCL11A gene polymorphism is associated with better clinical severity of ß-thalassemia.

DNMT3A and TET2; Potential Estimates of Generic DNA Methylation in Children and Adolescents with Obesity; Relation to Metabolic Dysregulation.

INTRODUCTION: The role of DNA methylation in metabolic dysregulation is emerging. However, the functional role of methylation in obesity and metabolic dysregulation is poorly understood. AIM: The aim of this study was to compare DNA methyltransferase-3A (DNMT3A) and ten-eleven translocase-2 (TET2) levels in children and adolescents with obesity to normal-weighed children and adolescents and to correlate them to various metabolic parameters. METHODS: Fifty children and adolescents with obesity were compared to 50 matched normal-weighed children and adolescents. Participants underwent assessment for anthropometric measurements, Tanner staging, acanthosis nigricans, and mean blood pressure percentile on three different occasions. TET2, DNMT3A, fasting lipids, and insulin were measured with calculation of the homeostatic model assessment insulin resistance (HOMA-IR). RESULTS: The median BMI SDS of the studied children and adolescents with obesity was 3.40, their mean TET2 was 178.40 ng/mL, and their mean DNMT3A was 2.18 ng/mL. TET2 is significantly lower (p = 0.009), while DNMT3A is significantly higher (p < 0.001) in children and adolescents with obesity than controls. Children and adolescents with obesity and insulin resistance have significantly lower TET2 (p = 0.012) and significantly higher DNMT3A (p = 0.013) than those without insulin resistance. Diastolic blood pressure percentile and HOMA-IR are positively correlated to DNMT3A (p < 0.001) and negatively correlated to TET-2 (p < 0.001). Multivariate logistic regression analysis revealed that TET2 and DNMT3A are independently associated with diastolic blood pressure percentile (p = 0.03 and p = 0.014, respectively) and HOMA-IR (p = 0.003 and p = 0.001, respectively). CONCLUSIONS: Children and adolescents with obesity have significantly higher DNMT3A and significantly lower TET2 than controls. This is more evident in those having insulin resistance than those without. DNMT3A and TET2 are independently associated with systemic hypertension and insulin resistance in children with obesity.

PD1 expression on bone marrow T-cells in newly diagnosed Egyptian AML patients: Correlation with hematological parameters, aberrant antigens expression, and response to induction therapy.

Background: Programed cell death protein 1 (PD-1) is a key mediator for the development of T cell exhaustion that develops in response to persistent antigen stimulation. Aim: In this study, we measured PD1 expression on CD3 positive bone marrow T-lymphocytes in newly diagnosis AML patients and its relation to clinical/ prognostic outcomes in addition to response to induction therapy (day 28). Methods: This study was conducted on 59 newly diagnosed AML patients and 20 healthy controls. Complete blood counts, flow cytometry using acute leukemia panel in addition to PD1 monoclonal antibodies were performed on bone marrow lymphocytes (CD3+), whereas cytogenetic/molecular studies were used to determine risk group. The patients' remission status following induction therapy was determined. Results: PD1 was brightly expressed in 91.5% of the cases than control sample with highly significant difference (P = .001). A cutoff of 3.5 for mean fluorescence intensity was used to divide patients into two groups (higher vs normal PD1 expression). A significant difference between the two groups regarding platelet count and aberrant CD7 expression (P = .007 and .023, respectively) was found. Those normally expressed PD1 respond better to induction therapy. Conclusion: PD1 expression on BM T-cells had a predictive value and providing an immunotherapeutic target for AML.

Detection of 14q32 rearrangements in multiple myeloma, using simultaneous FISH analysis combined with immunofluorescence.

BACKGROUND: 14q32 rearrangement has been identified as a recurrent hotspot of translocations in multiple myeloma (MM). The Fluorescence Immunophenotyping and Interphase Cytogenetics as a tool for the Investigation of Neoplasms (known as FICTION technique) for evaluation of chromosomal changes in MM. The aim of this work is to detect 14q32 rearrangement, using FICTION technique, on archival bone marrow (BM) slides of MM patients, and to study its prognostic value. METHOD: This study was conducted at Ain Shams University Hospital. The FICTION technique, which uses CD138 and dual color, and the break-apart 14q32 rearrangement probe, was performed on archived smears of BM slides for 50 MM patients at the time of diagnosis. RESULTS: A significantly higher percentage of cases were positive for 14q32 rearrangement by FICTION (32%) compared to fluorescence in situ hybridization (FISH) (12%) (p=0.04). Cases positive by FICTION for the rearrangement were designated as Group A, while negative cases were designated as Group B. Significantly lower Hb and CRP levels were found among Group B when compared to Group A patients (p=0.001 and 0.01, respectively). Serum albumin level and Bence Jones protein (BJP) significantly affect overall survival (OS) (p=0.01, 0.007, respectively). However, a statistically non-significant shorter mean survival time was found in positive cases through FICTION versus negative cases. CONCLUSION: FICTION technique provides a sensitive tool for establishing clonal plasma cells (PC) infiltration of BM aspirates, and is amenable for use on archived as well as fresh smears.