Tumor-derived cell lines have served as vital models to advance our understanding of oncogene function and therapeutic responses. Although substantial effort has been made to define the genomic constitution of cancer cell line panels, the transcriptome remains understudied. Here we describe RNA sequencing and single-nucleotide polymorphism (SNP) array analysis of 675 human cancer cell lines. We report comprehensive analyses of transcriptome features including gene expression, mutations, gene fusions and expression of non-human sequences. Of the 2,200 gene fusions catalogued, 1,435 consist of genes not previously found in fusions, providing many leads for further investigation. We combine multiple genome and transcriptome features in a pathway-based approach to enhance prediction of response to targeted therapeutics. Our results provide a valuable resource for studies that use cancer cell lines.

Monocytes from patients with sickle cell disease (SCD) are in an activated state. However, the mechanism of activation of monocytes in SCD is not known. Our studies showed that placenta growth factor (

Cell line misidentification, contamination and poor annotation affect scientific reproducibility. Here we outline simple measures to detect or avoid cross-contamination, present a framework for cell line annotation linked to short tandem repeat and single nucleotide polymorphism profiles, and provide a catalogue of synonymous cell lines. This resource will enable our community to eradicate the use of misidentified lines and generate credible cell-based data.

Sickle cell disease (SCD) results in chronic hypoxia and secondarily increased erythropoietin concentrations. Leukocytosis and activated monocytes are also observed in SCD in absence of infection or vaso-occlusion (steady state), the reasons for which are unknown. We found that erythroid cells produced placenta growth factor (PlGF), an angiogenic growth factor belonging to the vascular endothelial growth factor (VEGF) family, and its expression was induced in bone marrow CD34 ؉ progenitor cells in the presence of erythropoietin. Furthermore, the steady state circulating PlGF levels in subjects with severe SCD (at least 3 vasoocclusive crises [VOCs] per year) were 18.5 ؎ 1.2 pg/mL (n ‫؍‬ 9) compared with 15.5 ؎ 1.2 pg/mL (n ‫؍‬ 13) in those with mild SCD (fewer than 3 VOCs per year) and 11.3 ؎ 0.7 pg/mL (n ‫؍‬ 9) in healthy controls (P < .05), suggesting a correlation between PlGF levels and SCD severity. In addition, PlGF significantly increased mRNA levels of the proinflammatory cytochemokines interleukin-1␤, interleukin-8, monocyte chemoattractant protein-1, and VEGF in peripheral blood mononuclear cells (MNCs) of healthy subjects (n ‫؍‬ 4; P < .05). Expression of these same cytochemokines was significantly increased in MNCs from subjects with SCD at steady state (n ‫؍‬ 14), compared with healthy controls. Of the leukocyte subfractions, PlGF stimulated monocyte chemotaxis (P < .05, n ‫؍‬ 3). Taken together, these data show for the first time that erythroid cells intrinsically release a factor that can directly activate monocytes to increase inflammation. The baseline inflammation seen in SCD has always been attributed to sequelae secondary to the sickling phenomenon. We show that PlGF contributes to the inflammation observed in SCD and increases the incidence of vaso-occlusive events. IntroductionSickle cell disease (SCD) is characterized by sickling of red blood cells (RBCs) due to polymerization of sickle hemoglobin upon deoxygenation, resulting in vascular occlusion. Repeated sickling and oxygenation-deoxygenation damages RBC membranes and shortens their life span, causing hemolysis and anemia. Chronic hemolytic anemia, shortened life span of RBCs, and vascular occlusions are the hallmarks of the disease. 1,2 The bone marrow responds to hypoxia and anemia with an erythropoietic response, reflected by high circulating reticulocytes. 3,4 Another salient feature of SCD is leukocytosis that occurs despite absence of acute infection or inflammation. Activated monocytes, 5-7 endothelial cells, 5,7,8 neutrophils, 9,10 and the coagulation cascade 11,12 observed in SCD at steady state have been presumed to be secondary sequelae to the sickling phenomenon. 2 While activated leukocytes 13,14 have been shown to initiate and/or promote vaso-occlusion, 15 the reasons for leukocytosis, activation of monocytes and neutrophils, and increased adhesivity of endothelium at steady state are largely unknown.Activation of endothelial cells in SCD contributes to vascular occlusions. 5,7,8,16 Vascular endothelial growth factor (V...