Rabbit Anti-Human Histone H3 (phospho Thr32) Polyclonal antibody

Molecular alterations in the histone methyltransferase EZH2 and the antiapoptotic protein Bcl-2 frequently co-occur in diffuse large B-cell lymphoma (DLBCL). Because DLBCL tumors with these characteristics are likely dependent on both oncogenes, dual targeting of EZH2 and Bcl-2 is a rational therapeutic approach. We hypothesized that EZH2 and Bcl-2 inhibition would be synergistic in DLBCL. To test this, we evaluated the EZH2 inhibitor tazemetostat and the Bcl-2 inhibitor venetoclax in DLBCL cells, 3-dimensional lymphoma organoids, and patient-derived xenografts (PDXs). We found that tazemetostat and venetoclax are synergistic in DLBCL cells and 3-dimensional lymphoma organoids that harbor an EZH2 mutation and an IGH/BCL2 translocation but not in wild-type cells. Tazemetostat treatment results in upregulation of proapoptotic Bcl-2 family members and priming of mitochondria to BH3-mediated apoptosis, which may sensitize cells to venetoclax. The combination of tazemetostat and venetoclax was also synergistic in vivo. In DLBCL PDXs, short-course combination therapy resulted in complete remissions that were durable over time and associated with superior overall survival compared with either drug alone.

Cercospora coffeicola is the causal agent of brown eye spot, an important disease of coffee (Coffea arabica) in Brazil. However, atypical symptom as darker and larger lesions, named black spot, has been reported in field. In this study, we tested the hypothesis that the causal agent of black spot belongs to the same species pathogenic to brown eye spot. Nineteen strains obtained from diseased coffee found in the five largest coffee-producing states of Brazil were characterized by a combination of molecular phylogenic methods, using a multi-locus approach (internal transcribed spacer regions and intervening 5.8S nrRNAs, actin, calmodulin, histone H3, and translation elongation factor 1-alpha), analyses of morphological markers and pathogenicity. Strains from brown eye spot and black spot disease on coffee leaves formed a clade with C. coffeicola strain from Japan. All strains showed same morphological characteristics and caused brown eye spot symptoms in greenhouse. These results confirm that the species associated with brown eye spot and black spot disease on coffee leaves is C. coffeicola. Additionally, an epitype is proposed for C. coffeicola.