Bone marrow oxidative stress and specific antioxidant signatures in myelodysplastic syndromes
BLOOD ADVANCES
Authors: Picou, Frederic; Vignon, Christine; Debeissat, Christelle; Lachot, Sebastien; Kosmider, Olivier; Gallay, Nathalie; Foucault, Amelie; Estienne, Marie-Helene; Ravalet, Noernie; Bene, Marie C.; Domenech, Jorge; Gyan, Emmanuel; Fontenay, Michaels; Herault, Olivier
Abstract
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders with an inherent tendency for transformation in secondary acute myeloid leukemia. This study focused on the redox metabolism of bone marrow (BM) cells from 97 patients compared with 25 healthy controls. The level of reactive oxygen species (ROS) was quantified by flow cytometry in BM cell subsets as well as the expression level of 28 transcripts encoding for major enzymes involved in the antioxidant cellular response. Our results highlight increased ROS levels in BM nonlymphoid cells and especially in primitive CD34(pos)CD381(ow) progenitor cells. Moreover, we identified a specific antioxidant signature, dubbed "antioxidogram," for the different MDS subgroups or secondary acute myeloblastic leukemia (sAML). Our results suggest that progression from MDS toward sAML could be characterized by 3 successive molecular steps: (1) overexpression of enzymes reducing proteic disulfide bonds (MDS with <5% BM blasts [GLRX family]); (2) increased expression of enzymes detoxifying H2O2 (MDS with 5% to 19% BM blasts [PRDX and GPX families]); and finally (3) decreased expression of these enzymes in sAML. The antioxidant score (AO-Score) defined by logistic regression from the expression levels of transcripts made it possible to stage disease progression and, interestingly, this AO-Score was independent of the revised International Scoring System. Altogether, this study demonstrates that MDS and sAML present an important disturbance of redox metabolism, especially in BM stem and progenitor cells and that the specific molecular antioxidant response parameters (antioxidogram, AO-Score) could be considered as useful biomarkers for disease diagnosis and follow-up.
Regulatory mechanisms of leaf color change in Acer pictum subsp. mono
GENOME
Authors: Ge, Wei; Wang, Xiaoxiao; Li, Jianyi; Zhu, Wenpeng; Cui, Jinteng; Zhang, Kezhong
Abstract
Acer pictum subsp. mono is a colored leaf tree with vital ornamental and economic value. However, insufficient color change and early leaf fall in cities restrict its ornamental value. In this research, green and red leaves from wild A. p. subsp. mono were collected to study the regulatory mechanisms of leaf color change. Through the determination of plant physiological indexes, we found that the photosynthetic pigment content in red leaves decreased significantly compared with green leaves, while the anthocyanin content and antioxidant activity increased significantly compared with green leaves during the leaf color change process. Using transcriptome sequencing, we found more than 5500 differentially expressed genes, most of which were up-regulated. Many of the differentially expressed genes are involved in the anthocyanin metabolic pathway. The expression patterns of 15 key genes were investigated by quantitative real-time polymerase chain reaction. Among these genes, AmDFR and PAL1 are significant genes involved in the anthocyanin metabolic pathway, and CIPKs2, CIPKs6, CMLs1, CMLs38, AmGST1, AmGST2, GPX3, CBF, AmAPX, AmSOD, POD5, AmGR, and PSBY might be stress response genes that indirectly regulated the anthocyanin accumulation. The results showed that these genes play vital roles in the leaf color change of A. p. subsp. mono. This research will be helpful in further study of the molecular regulatory mechanisms of leaf color change and for the improvement of colored leaf plants.