Blast cells from 20 patients with acute leukemia (13 diagnosed myeloblastic and 7 as lymphoblastic, using the FAB classification) were studied using antibodies to lineage-specific differentiation markers. The phenotypic findings were usually consistent with the clinical diagnosis. However, examples were encountered where individual blast cells had a cytoplasmic marker of one lineage and a surface marker of a different lineage (lineage infidelity). Six examples of intramyeloid (two different myeloid lineages in the same cell) and three examples of interlineage infidelity (myeloid and lymphoid markers in the same blast cell) were encountered. No doubly marked cells were found in control material consisting of normal marrow cells, marrow regenerating after transplantation, or multilineage colonies derived from marrow in culture. A significant trend was observed relating the presence of lineage infidelity and failure of remission-induction. The data are interpreted as support for abnormal gene expression in leukemia.
Stabilization of p53 in erythroid precursors in response to nucleosomal stress underlies the hypoplastic anemia in myelodysplastic syndromes (MDS) with chromosome 5q deletion [del(5q)]. We investigated whether cenersen, a clinically active 20-mer antisense oligonucleotide complementary to TP53 exon10, could suppress p53 expression and restore erythropoiesis in del(5q) MDS. Cenersen treatment of ribosomal protein S-14-deficient erythroblasts significantly reduced cellular p53 and p53-up-regulated modulator of apoptosis expression compared with controls, accompanied by a significant reduction in apoptosis and increased cell proliferation. In a two-stage erythroid differentiation assay, cenersen significantly suppressed nuclear p53 in bone marrow CD34+ cells isolated from patients with del(5q) MDS, whereas erythroid burst recovery increased proportionally to the magnitude of p53 suppression without evidence of del(5q) clonal suppression (r = −0.6; P = 0.005). To explore the effect of p53 suppression on erythropoiesis in vivo, dexamethasone, a glucocorticoid receptor-dependent p53 antagonist, was added to lenalidomide treatment in eight lower-risk, transfusion-dependent, del(5q) MDS patients with acquired drug resistance. Transfusion independence was restored in five patients accompanied by expansion of erythroid precursors and decreased cellular p53 expression. We conclude that targeted suppression of p53 could support effective erythropoiesis in lenalidomide-resistant del(5q) MDS.
D-Dimer results have high NPV and sensitivity for PE in oncologic patients and, if negative, can be used to exclude PE in this population. Combining the assay with clinical symptoms and signs did not substantially change NPV, PPV, sensitivity, or specificity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.