miR‑29 promoter and enhancer methylation identified by pyrosequencing in Burkitt lymhoma cells: Interplay between MYC and miR‑29 regulation.

Deregulation of microRNA expression plays a significant role in several cancer types including Burkitt lymphoma (BL). MicroRNA genes may be regulated through epigenetic mechanisms, such as specific histone modifications and/or DNA methylation of CpG islands in promoter regions, or by regions that are located next to microRNA genes. Given the regulatory role of MYC in miR‑29 expression, methylation as an additional mechanism for miR‑29 silencing was investigated.

IKZF1 deletion and co-occurrence with other aberrations in a child with chronic myeloid leukemia progressing to acute lymphoblastic leukemia.

Chronic myeloid leukemia (CML) is a rare disease in children. Different from that in adults, childhood CML involves transformative events occurring over a short time period. CML transformation to lymphoid blast phase (BP) is associated with copy number abnormalities, characteristic of BCR-ABL1 positive acute lymphoblastic leukemia, but not of CML in the chronic phase.

MiR-29 silencing modulates the expression of target genes related to proliferation, apoptosis and methylation in Burkitt lymphoma cells.

Purpose: Burkitt lymphoma (BL) is a B-cell lymphoma frequently diagnosed in children. It is characterized by MYC translocations, which lead to the constitutive expression of the MYC oncogene. MYC contributes to miR-29 repression through an E-box MYC binding site on the miR-29b-1/miR-29a promoter region.

miR-17-92 cluster components analysis in Burkitt lymphoma: overexpression of miR-17 is associated with poor prognosis.

Burkitt lymphoma (BL) is an aggressive B cell lymphoma characterized by the reciprocal translocation of the c-Myc gene with immunoglobulin genes. Recently, MYC has been shown to maintain the neoplastic state via the miR-17-92 microRNA cluster that suppresses chromatin regulatory genes and the apoptosis regulator Bim. However, the expression and prognostic impact of miR-17-92 members in pediatric BL (pBL) are unknown.

Dual inhibition of histone deacetylases and phosphoinositide 3-kinases: effects on Burkitt lymphoma cell growth and migration.

Burkitt lymphoma is a highly aggressive non-Hodgkin lymphoma that is characterized by MYC deregulation. Recently, the PI3K pathway has emerged as a cooperative prosurvival mechanism in Burkitt lymphoma. Despite the highly successful results of treatment that use high-dose chemotherapy regimens in pediatric Burkitt lymphoma patients, the survival rate of pediatric patients with progressive or recurrent disease is low.

An unusual long-term outcome of a child with primary myelofibrosis harboring a JAK2 mutation.

We report an extremely rare case of a female child who presented the onset of primary myelofibrosis (PMF) harboring JAK2 (Janus Kinase 2 gene) mutation (JAK2V617F) when she was 15 months old. She was monitored over 25 years, a period in which she was treated with spleen radiotherapy and recombinant interferon α. She also underwent splenectomy when she was 13 years old, due to massive splenomegaly, anemia and various infection disease episodes.

Deregulation of DNMT1, DNMT3B and miR-29s in Burkitt lymphoma suggests novel contribution for disease pathogenesis.

Methylation of CpG islands in promoter gene regions is frequently observed in lymphomas. DNA methylation is established by DNA methyltransferases (DNMTs). DNMT1 maintains methylation patterns, while DNMT3A and DNMT3B are critical for de novo DNA methylation.

Quantitative analysis of CDKN2A methylation, mRNA, and p16(INK4a) protein expression in children and adolescents with Burkitt lymphoma: biological and clinical implications.

CDKN2A is a tumor suppressor gene critical in the cell cycle regulation. Little is known regarding the role of CDKN2A methylation in the pathogenesis of Burkitt lymphoma (BL). CDKN2A methylation was investigated using pyrosequencing in 51 tumor samples.

Langerhans cell histiocytosis: differences and similarities in long-term outcome of paediatric and adult patients at a single institutional centre.

Purpose: This study determined the frequency of clinical features, reactivations, sequelae, mortality, and overall survival (OS) and compared paediatric with adult Langerhans cell histiocytosis (LCH) patients.

Materials And Methods: Ninety patients (60 paediatric and 30 adults) with LCH treated during 28 years were analysed retrospectively.

Results: Craniofacial lesion was the most frequent lesion at LCH presentation in children and adults.

Histone deacetylase inhibitor prevents cell growth in Burkitt's lymphoma by regulating PI3K/Akt pathways and leads to upregulation of miR-143, miR-145, and miR-101.

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma more common in children comprising one third of pediatric non-Hodgkin lymphoma cases. The recent discovery in BL pathogenesis highlighted the activation of PI3K pathway in cooperation with Myc in the development of BL. In this study, we demonstrated that PI3K/Akt pathway is a target to histone deacetylase inhibitor (HDACi) in BL cells.

Lymphoma subtype incidence rates in children and adolescents: first report from Brazil.

Background: Lymphoma is the third most common pediatric malignancy. The purpose of this study was to analyze the incidence rates of lymphoma in children and adolescents in Brazil.

Methods: All cases of Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), and Burkitt lymphoma (BL) were extracted from 14 population-based cancer registries (PBCRs) from 2000 to 2005, and included children and adolescents 0-19 years old.

Histone deacetylase inhibitor potentiates chemotherapy-induced apoptosis through Bim upregulation in Burkitt's lymphoma cells.

Purpose: Although polychemotherapy regiments have improved clinical outcome for Burkitt's lymphoma (BL) patients, salvage treatment of patients with refractory disease remains very poor. Combined therapies protocols have been emerging to improve treatment strategies to circumvent responseless BL patients. We evaluate the cell death effect of histone deacetylase inhibitor (HDACI) combined with etoposide (VP-16) and cisplatin (CDDP) on BL cell lines.

p53 flow cytometry evaluation in leukemias: correlation to factors affecting clinical outcome.

p53 is a cell cycle checkpoint control protein that assesses DNA damage and acts as a transcription factor regulating genes, which control cell growth, DNA repair, and apoptosis. p53 mutations have been found in a wide variety of different cancers including flow cytometric assessment of p53 protein expression using anti-p53 monoclonal antibodies. We studied p53 protein expression by flow cytometry (FC) assay in 223 blood and/or bone marrow samples from 72 patients with chronic myeloid leukemia (CML): 54 in chronic phase (CML-CP), 7 in accelerated phase (CML-AP), and 11 in blastic phase (CML-BP); 64 patients with chronic lymphoid leukemia (CLL): (34 at diagnosis, 21 in previously treated, and 9 with Richter's syndrome); 44 patients with acute lymphoid leukemia (ALL): 36 at diagnosis and 8 in relapse; and 43 acute myeloid leukemia (AML): 27 de novo, 7 in relapse, and 9 secondary.

Insights into apoptosis mechanisms induced by DNA-damaging agents in Burkitt's lymphoma cells.

p53 protein induces cell cycle arrest, DNA repair, or apoptosis of damaged cells. Loss of wild-type p53 (wt-p53) function was shown to be associated with upregulation of survivin and resistance to therapy. Here we investigated the effects of DNA-damage agents in inducing apoptosis and cell cycle arrest, and modulation of survivin levels in two Burkitt's lymphoma (BL) cell lines with different p53 mutations.

Modulation of reactive oxygen species by antioxidants in chronic myeloid leukemia cells enhances imatinib sensitivity through survivin downregulation.

Survivin, a member of the inhibitor of apoptosis protein family and a target for new drugs, is modulated by reactive oxygen species in several types of neoplasms including leukemias. The aim of this study is to find mechanisms to enhance sensitivity to imatinib in imatinib-responsive cells. In this study, we demonstrated through fluorescein isothiocyanate-labeled annexin V for apoptotic cells detection and western blotting that by inhibiting catalase activity, imatinib apoptosis induction was significantly enhanced (P<0.

Plasma Epstein-Barr viral load predicting response after chemotherapy for post-transplant lymphoproliferative disease.

Transplant patients are particularly at risk of developing B post-transplant lymphoproliferative disease (PTLD) related to intensive immunosuppressive treatment to prevent graft rejection. In EBV-positive PTLDs, EBV-DNA can be found in the patients' peripheral blood. Several methods have been described to assess peripheral blood EBV viral load.

Clinical and demographic characteristics of Epstein-Barr virus-associated childhood Burkitt's lymphoma in Southeastern Brazil: epidemiological insights from an intermediate risk region.

We studied a group of 54 children with Burkitt's lymphoma from Southeastern Brazil, where epidemiological status of Burkitt's lymphoma is poorly understood. Epstein-Barr virus association showed an intermediate frequency (~60%) between endemic and sporadic subtypes. Median age was five years.

Epstein-Barr virus (EBV) detection and typing by PCR: a contribution to diagnostic screening of EBV-positive Burkitt's lymphoma.

Background: Epstein-Barr virus (EBV) is associated to the etio-pathogenesis of an increasing number of tumors. Detection of EBV in pathology samples is relevant since its high prevalence in some cancers makes the virus a promising target of specific therapies. RNA in situ hybridization (RISH) is the standard diagnostic procedure, while polymerase chain reaction (PCR)-based methods are used for strain (EBV type-1 or 2) distinction.

Coexpression of p53 protein and MDR functional phenotype in leukemias: the predominant association in chronic myeloid leukemia.

Background: One of the best characterized resistance mechanisms of leukemias is multidrug resistance (MDR) mediated by P-glycoprotein (Pgp) and multidrug-resistant related protein (MRP). In addition to Pgp and MRP, p53 mutation or inactivation might play a relevant role in therapeutic failure. Some studies have demonstrated that Pgp and MRP may be activated in association with overexpression of mutant or inactivated p53 protein.

Treatment of children with B-cell non-Hodgkin's lymphoma in developing countries: the experience of a single center in Brazil.

Purpose: To treat non-Hodgkin's B-cell lymphoma (B-NHL) in children with manageable toxicity-related morbidity and without any decrease in survival.

Patients And Methods: Between January 1998 and April 2003, 53 consecutive patients (age 16 years or less) from a single institution were enrolled. The patients were stratified by risk factors (stage and LDH level) and treated with a BFM 86/90 (Berlin-Frankfurt-Münster)-based protocol with reduction of the methotrexate dose from 5 mg/m to 2 mg/m.

Geographic variation in Epstein-Barr virus-associated Burkitt's lymphoma in children from Brazil.

In developing countries, BL has a strong association with EBV infection during childhood. In South America, the data have shown an EBV association intermediate between that reported in the United States (30%) and that in equatorial Africa (95%). Early age at EBV infection and lower socioeconomic status have been related to increased EBV-associated BL in developing countries.

DNA sequence profile of TP53 gene mutations in childhood B-cell non-Hodgkin's lymphomas: prognostic implications.

Objectives: The TP53 gene encodes a nuclear protein implicated in the regulation of the cell cycle, DNA repair, and apoptosis. TP53 mutations and other alterations have been described in numerous types of tumors, and some of these have been associated with poor prognosis. The aim of this study was to characterize TP53 mutations in childhood B non-Hodgkin's lymphoma, their correlation with clinical prognostic factors and response to therapy.

Burkitt-like lymphoma in an infant: a case report.

Childhood non-Hodgkin's lymphomas, including Burkitt and Burkitt-like, are rarely diagnosed in infants. A case of B-cell lymphoma in a 13-month-old girl with extensive abdominal disease, ascites, pleural effusion, and tumor lysis syndrome is reported. Phenotypic analysis showed a germinal center B-cell phenotype, and a B-cell clonality was confirmed by polymerase chain reaction.