MLLT10, a 24 exons gene at 10p12, is known in leukemogenesis as partner of MLL or PICALM and recently NAP1L1. We identified HNRNPH1 and DDX3X, genes involved in RNA processing, as new MLLT10 partners in 2 cases of pediatric NOTCH1 positive T-ALL. HNRNPH1/5q35 encodes for a member of the ubiquitously expressed heterogeneous nuclear ribonucleoprotein (hnRNP) subfamily of RNA binding protein. DDX3X/Xp11.3, belongs to the big family of RNA helicases with a DEAD box domain.
New MLLT10 gene recombinations in pediatric T-acute lymphoblastic leukemia.
Disease
View SamplesWe have cloned and characterized a fusion gene NUP98/HHEX1 resulting from t(7;10) from a patient with acute myeloid leukemia (AML). As NUP98/HHEX acts as an aberrant transcriptional activator, putative targets were searched upon transient expression of the fusion in primary murine bone marrow cells.
Leukemogenic mechanisms and targets of a NUP98/HHEX fusion in acute myeloid leukemia.
No sample metadata fields
View SamplesAML with mutated NPM1 usually carries normal karyotype (NK) but it may harbor chromosomal aberrations whose significance remains unclear. We addressed this question in 631 AML patients with mutated/cytoplasmic NPM1. An abnormal karyotype (AK) was present in 93/631 cases (14.7%), the most frequent abnormalities being +8, +4, -Y, del(9q), +21. Chromosome aberrations in NPM1-mutated AML were similar to, but occurred less frequently than additional chromosome changes found in other AML with recurrent cytogenetic abnormalities according to WHO classification. Four of the 31 NPM1-mutated AML patients karyotyped at different time points had NK at diagnosis but AK at relapse: del(9q) (n=2), t(2;11) (n=1), inv(12) (n=1).
AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features.
No sample metadata fields
View SamplesApproximately one third of acute myeloid leukemias (AMLs) are characterized by aberrant cytoplasmic localization of Nucleophosmin (NPMc+ AML), consequent to mutations in the NPM putative nucleolar localization signal. These events are mutually exclusive with the major AML-associated chromosomal rearrangements, and are frequently associated with normal karyotype, Fms-like tyrosine kinase (FLT3) mutations and multilineage involvement. We report the gene expression profiles of 78 de novo AMLs (72 with normal karyotype; 6 with non-major chromosomal abnormalities) that were characterized for the subcellular localization and mutation status of NPM. Unsupervised clustering clearly separated NPMc+ from NPMc- AMLs, regardless of the presence of FLT3 mutations or non-major chromosomal rearrangements, supporting the concept that NPMc+ AML represents a distinct entity. The molecular signature of NPMc+ AML includes up-regulation of several genes putatively involved in the maintenance of a stem cell phenotype, suggesting that NPMc+ AML may derive from a multipotent hematopoietic progenitor.
Acute myeloid leukemia bearing cytoplasmic nucleophosmin (NPMc+ AML) shows a distinct gene expression profile characterized by up-regulation of genes involved in stem-cell maintenance.
Specimen part
View SamplesGEP class prediction in association with CI-FISH (42 candidate genes) and patient MRD stratification
Linking genomic lesions with minimal residual disease improves prognostic stratification in children with T-cell acute lymphoblastic leukaemia.
Specimen part, Disease, Disease stage
View SamplesWe used microarrays to assess gene expression changes in cells with siRNA-mediated knockdown of OPG compared to normal cells. Furthermore, we used microarrays to assess gene expression in cells treated with either RANKL or TRAIL compared to vehicle-treated cells.
No influence of OPG and its ligands, RANKL and TRAIL, on proliferation and regulation of the calcification process in primary human vascular smooth muscle cells.
Specimen part, Treatment
View SamplesIn Drosophila, PIWI proteins and bound PIWI interacting RNAs (piRNAs) form the core of a small RNA mediated defense system against selfish genetic elements. Within germline cells piRNAs are processed from piRNA clusters and transposons to be loaded into Piwi/Aubergine/AGO3 and a subset of piRNAs undergoes target dependent amplification. In contrast, gonadal somatic support cells express only Piwi, lack signs of piRNA amplification and exhibit primary piRNA biogenesis from piRNA clusters. Neither piRNA processing/loading nor Piwi mediated target silencing is understood at the genetic, cellular or molecular level. We developed an in vivo RNAi assay for the somatic piRNA pathway and identified the RNA helicase Armitage, the Tudor domain containing RNA helicase Yb and the putative nuclease Zucchini as essential factors for primary piRNA biogenesis. Lack of any of these proteins leads to transposon de-silencing, to a collapse in piRNA levels and to a failure in Piwi nuclear accumulation. We show that Armitage and Yb interact physically and co-localize in cytoplasmic Yb-bodies, which flank P-bodies. Loss of Zucchini leads to an accumulation of Piwi and Armitage in Yb-bodies indicating that Yb-bodies are sites of primary piRNA biogenesis. Overall design: small RNA libraries were prepared from Piwi immuno-precipitates of five different genotypes
An in vivo RNAi assay identifies major genetic and cellular requirements for primary piRNA biogenesis in Drosophila.
Subject
View SamplesThe aim of the study was to illucidate how BAFF mediates B cell survival and growth through the identification of BAFF-regulated genes.
BAFF controls B cell metabolic fitness through a PKC beta- and Akt-dependent mechanism.
No sample metadata fields
View SamplesAirway epithelium is the initial point of host-pathogen interaction in Pseudomonas aeruginosa infection, an important pathogen in cystic fibrosis and nosocomial pneumonia. We used global gene expression analysis to determine airway epithelial transcriptional responses dependent on matrilysin (MMP-7) and stromelysin-2 (MMP-10), two matrix metalloproteinases induced by acute P. aeruginosa pulmonary infection. Extraction of Differential Gene Expression (EDGE) analysis of gene expression changes in P. aeruginosa infected organotypic tracheal epithelial cell cultures from wildtype, Mmp7-/-, and Mmp10-/- mice identified 2,089 matrilysin-dependent and 1,628 stromelysin-2-dependent genes that were differentially expressed. Key node network analysis showed that these MMPs controlled distinct gene expression programs involved in proliferation, cell death, immune responses, and signal transduction, among other host defense processes. Our results demonstrate discrete roles for these MMPs in regulating epithelial responses to pseudomonas infection and show that a global genomics strategy can be used to assess MMP function.
Individual matrix metalloproteinases control distinct transcriptional responses in airway epithelial cells infected with Pseudomonas aeruginosa.
No sample metadata fields
View SamplesThis study examines the innate immune response of human pluripotent stem cell derived airway epithelium. Immune challenge was performed with TNF-alpha or bacterial lipopolysaccharide (LPS)
Innate immune response of human pluripotent stem cell-derived airway epithelium.
Specimen part, Treatment
View Samples