Long-Term Outcomes of Childhood Acute Lymphocytic Leukemia Treated with Adapted Berlin-Frankfurt-Münster (BFM) Protocols: A Multicentric Analysis from a Developing Country.

Introduction: The objective of the current study was to determine the survival probabilities of children and adolescents with acute lymphocytic leukemia treated with adapted Berlin-Frankfurt-Münster (BFM) protocols and compare our results with the original BFM reports.

Methods: This retrospective study included 695 patients up to 19 years old treated with adapted BFM protocols between 1997 and 2018 in four hospitals in Rio de Janeiro. The 1997-2007 and 2008-2018 cohorts were analyzed separately.

Recently Evolved Enhancers Emerge with High Interindividual Variability and Less Frequently Associate with Disease.

Mutations in non-coding regulatory DNA such as enhancers underlie a wide variety of diseases including developmental disorders and cancer. As enhancers rapidly evolve, understanding their function and configuration in non-human disease models can have important clinical applications. Here, we analyze enhancer configurations in tissues isolated from the common marmoset, a widely used primate model for human disease.

Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients.

Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which changes are relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements (GREs) at cell type resolution in the brains of multiple primate species spanning most of primate evolution.

Transcriptomic and Epigenomic Profiling of Histone Deacetylase Inhibitor Treatment Reveals Distinct Gene Regulation Profiles Leading to Impaired Neutrophil Development.

The clinical use of histone deacetylase inhibitors (HDACi) for the treatment of bone marrow failure and hematopoietic malignancies has increased dramatically over the last decades. Nonetheless, their effects on normal myelopoiesis remain poorly evaluated. Here, we treated cord blood derived CD34+ progenitor cells with two chemically distinct HDACi inhibitors MS-275 or SAHA and analyzed their effects on the transcriptome (RNA-seq), epigenome (H3K27ac ChIP-seq) and functional and morphological characteristics during neutrophil development.

AML Subtype Is a Major Determinant of the Association between Prognostic Gene Expression Signatures and Their Clinical Significance.

Relapse in acute myeloid leukemia (AML) may result from variable genetic origins or convergence on common biological processes. Exploiting the specificity and sensitivity of regulatory DNA, we analyze patient samples of multiple clinical outcomes covering various AML molecular subtypes. We uncover regulatory variation among patients translating into a transcriptional signature that predicts relapse risk.

Epigenetic drug screen identifies the histone deacetylase inhibitor NSC3852 as a potential novel drug for the treatment of pediatric acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a heterogeneous disease regarding morphology, immunophenotyping, genetic abnormalities, and clinical behavior. The overall survival rate of pediatric AML is 60% to 70%, and has not significantly improved over the past two decades. Children with Down syndrome (DS) are at risk of developing acute megakaryoblastic leukemia (AMKL), which can be preceded by a transient myeloproliferative disorder during the neonatal period.

Is the worst of the epidemic over? Back calculation of HIV seroprevalence in The Netherlands.

This article calculates back the HIV seroprevalence in the Netherlands from AIDS cases notified 1982-1990 and rates of progression from HIV to AIDS adopted from American studies. It discusses a number of problems, such as changing AIDS definitions and the possible impact of AZT treatment. We estimate that the Netherlands had approximately 6762 HIV seropositives by the end of 1988, which is considerably lower than earlier expectations.

[Estimate of the number of HIV-seropositive persons in The Netherlands; implications for the evolution of the AIDS epidemic].

In this article we estimate the total number of HIV seropositives in the Netherlands with an extended version of the Fast Back Calculation model. As a result we found between 5500 and 6500 seropositives for the end of 1987. This is considerably lower than earlier expectations.