Morfoanatomia e histoquímica da semente de sororoca (Phenakospermum guyannense (Rich.) Endl. - Strelitziaceae)

Phenakospermum guyannense, popularly known in the Amazon as sororoca, is usually found along rivers and in ombrophilous environments. The objective of this study was to describe the morpho-anatomy and histochemistry of mature seeds of P. guyannense collected at the Urubuí Waterfall, Presidente Figueiredo, Amazonas state, Brazil. Seed anatomy was studied using a light and a scanning electron microscopes (SEM). Histochemical tests were performed to identify phenolic compounds, starch, protein and lipids. The mature seed of P. guyannense is stenospermic, with a black seed coat composed of several layers of different cell types, with most containing phenolic compounds. The hilum is punctiform, surrounded by cells, which form the aryl. The endosperm is solid, formed by tetrahedral cells containing starch and protein. The embryo, which is cylindrical and located in the proximal region, is basal capitate, with cells containing lipids and proteins and is composed of a slightly dilated hypocotyl-radicle axis. The haustorium is flattened and located in the distal region

Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies

The BCL2 inhibitor venetoclax has been approved to treat different hematological malignancies. Since there is no common genetic alteration causing resistance to venetoclax in CLL and B cell lymphoma, we asked if epigenetic events might be involved in venetoclax resistance. Therefore, we employed whole exome sequencing, methylated DNA immunoprecipitation sequencing and genome wide CRISPR/Cas9 screening to investigate venetoclax resistance in aggressive lymphoma and high-risk CLL patients. We identified a regulatory CpG island within the PUMA promoter which is methylated upon venetoclax treatment, mediating PUMA downregulation on transcript and protein level. PUMA expression and sensitivity towards venetoclax can be restored by inhibition of methyltransferases. We can demonstrate that loss of PUMA results in metabolic reprogramming with higher OXPHOS and ATP production, resembling the metabolic phenotype that is seen upon venetoclax resistance. While PUMA loss is specific for acquired venetoclax resistance but not for acquired MCL1 resistance and is not seen in CLL patients after chemotherapy-resistance, BAX is essential for sensitivity towards both venetoclax and MCL1 inhibition. As we found loss of BAX in Richter's syndrome patients after venetoclax failure, we defined BAX-mediated apoptosis to be critical for drug resistance but not for disease progression of CLL into aggressive DLBCL in vivo. A compound screen revealed TRAIL-mediated apoptosis as a target to overcome BAX deficiency. Furthermore, antibody or CAR T cells eliminated venetoclax resistant lymphoma cells, paving a clinically applicable way to overcome venetoclax resistance