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Precursor T-cell neoplasms (T-ALL/LBL) are aggressive hematological malignancies that arise from the malignant transformation of immature thymocytes. Despite the JAK/STAT pathway is recurrently altered in these neoplasms, there are not pharmacological inhibitors officially approved for the treatment of T-ALL/LBL patients that present oncogenic JAK/STAT pathway mutations. In the effort to identify potential therapeutic targets for those patients, we followed an alternative approach and focused on their transcriptional profile. We combined the analysis of molecular data from T-ALL/LBL patients with the generation of hematopoietic cellular models to reveal that JAK/STAT pathway mutations are associated with an aberrant transcriptional profile. Specifically, we demonstrate that JAK/STAT pathway mutations induce the overexpression of the PIM1 gene. Moreover, we show that the pan-PIM inhibitor, PIM447, significantly reduces the leukemogenesis, as well as the aberrant activation of c-MYC and mTOR pathways in cells expressing different JAK/STAT pathway mutations, becoming a potential therapeutic opportunity for a relevant subset of T-ALL/LBL patients.
Pubmed ID: 39033228
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Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsA software package to analyze next-generation resequencing data. The toolkit offers a wide variety of tools, with a primary focus on variant discovery and genotyping as well as strong emphasis on data quality assurance. Its robust architecture, powerful processing engine and high-performance computing features make it capable of taking on projects of any size. This software library makes writing efficient analysis tools using next-generation sequencing data very easy, and second it's a suite of tools for working with human medical resequencing projects such as 1000 Genomes and The Cancer Genome Atlas. These tools include things like a depth of coverage analyzers, a quality score recalibrator, a SNP/indel caller and a local realigner. (entry from Genetic Analysis Software)
View all literature mentionsDatabase as central repository for both single base nucleotide substitutions and short deletion and insertion polymorphisms. Distinguishes report of how to assay SNP from use of that SNP with individuals and populations. This separation simplifies some issues of data representation. However, these initial reports describing how to assay SNP will often be accompanied by SNP experiments measuring allele occurrence in individuals and populations. Community can contribute to this resource.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented on January 19, 2022.
View all literature mentionsInternational collaboration producing an extensive public catalog of human genetic variation, including SNPs and structural variants, and their haplotype contexts, in an effort to provide a foundation for investigating the relationship between genotype and phenotype. The genomes of about 2500 unidentified people from about 25 populations around the world were sequenced using next-generation sequencing technologies. Redundant sequencing on various platforms and by different groups of scientists of the same samples can be compared. The results of the study are freely and publicly accessible to researchers worldwide. The consortium identified the following populations whose DNA will be sequenced: Yoruba in Ibadan, Nigeria; Japanese in Tokyo; Chinese in Beijing; Utah residents with ancestry from northern and western Europe; Luhya in Webuye, Kenya; Maasai in Kinyawa, Kenya; Toscani in Italy; Gujarati Indians in Houston; Chinese in metropolitan Denver; people of Mexican ancestry in Los Angeles; and people of African ancestry in the southwestern United States. The goal Project is to find most genetic variants that have frequencies of at least 1% in the populations studied. Sequencing is still too expensive to deeply sequence the many samples being studied for this project. However, any particular region of the genome generally contains a limited number of haplotypes. Data can be combined across many samples to allow efficient detection of most of the variants in a region. The Project currently plans to sequence each sample to about 4X coverage; at this depth sequencing cannot provide the complete genotype of each sample, but should allow the detection of most variants with frequencies as low as 1%. Combining the data from 2500 samples should allow highly accurate estimation (imputation) of the variants and genotypes for each sample that were not seen directly by the light sequencing. All samples from the 1000 genomes are available as lymphoblastoid cell lines (LCLs) and LCL derived DNA from the Coriell Cell Repository as part of the NHGRI Catalog. The sequence and alignment data generated by the 1000genomes project is made available as quickly as possible via their mirrored ftp sites. ftp://ftp.1000genomes.ebi.ac.uk ftp://ftp-trace.ncbi.nlm.nih.gov/1000genomes
View all literature mentionsA platform-independent, technology-independent software tool for identifying SNPs and indels in massively parallel sequencing of individual and pooled samples. Given data for a single sample, VarScan identifies and filters germline variants based on read counts, base quality, and allele frequency. Given data for a tumor-normal pair, VarScan also determines the somatic status of each variant (Germline, Somatic, or LOH) by comparing read counts between samples. (entry from Genetic Analysis Software)
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsAmerican chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.
View all literature mentionsAn efficient software tool to utilize update-to-date information to functionally annotate genetic variants detected from diverse genomes (including human genome hg18, hg19, as well as mouse, worm, fly, yeast and many others). Given a list of variants with chromosome, start position, end position, reference nucleotide and observed nucleotides, ANNOVAR can perform: 1. gene-based annotation. 2. region-based annotation. 3. filter-based annotation. 4. other functionalities. (entry from Genetic Analysis Software)
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsCompany provides laboratories worldwide with analytical instruments and supplies, clinical and diagnostic testing services, consumables, applications and expertise in life sciences and applied chemical markets.
View all literature mentionsGraph-based alignment of next generation sequencing reads to a population of genomes.
View all literature mentionsSoftware application for assembling of RNA-Seq alignments into potential transcripts. It enables improved reconstruction of a transcriptome from RNA-seq reads. This transcript assembling and quantification program is implemented in C++ .
View all literature mentionsCommercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.
View all literature mentionsAn Antibody supplier
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
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