A5049170518- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Chronic Lymphocytic Leukemia Research
- Virus-based gene therapy research
- Chronic Myeloid Leukemia Treatments
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Lymphoma Diagnosis and Treatment
- DNA Repair Mechanisms
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Cancer Genomics and Diagnostics
- Hematopoietic Stem Cell Transplantation
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- RNA Interference and Gene Delivery
- Chromosomal and Genetic Variations
- Immune Cell Function and Interaction
- Biochemical and Molecular Research
- RNA modifications and cancer
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer therapeutics and mechanisms
Center for Cancer Research
2016-2025
National Cancer Institute
2016-2025
National Institutes of Health
2015-2024
Institut thématique Génétique, génomique et bioinformatique
2017-2023
Leukemia Research Foundation
2018
Pediatric Oncology Group
2015
University of North Carolina at Chapel Hill
2014
University of Wisconsin–Madison
2014
Johns Hopkins University
2007-2014
Walter Reed National Military Medical Center
1989-2007
We have identified the human gene, SCL. discovered this gene because of its involvement in a chromosomal translocation associated with occurrence stem cell leukemia manifesting myeloid and lymphoid differentiation capabilities. Here we report sequence cDNA for normal SCL transcript, as well an aberrant fusion transcript produced leukemic cells. Although different at their 3' untranslated regions, both cDNAs predict protein primary amino acid homology to previously described amphipathic...
A fusion complementary DNA in the T cell line HSB-2 elucidates a provocative mechanism for disruption of putative hematopoietic transcription factor SCL . The cDNA results from an interstitial deletion between previously unknown locus, SIL ( interrupting locus), and 5′ untranslated region Similar to 1;14 translocations, this disrupts regulatory region. This event is probably mediated by V-(D)-J recombinase activity, although neither locus immunoglobulin or receptor. Two other lines, CEM RPMI...
Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of HOX genes, underlying mechanisms remain elusive. Here, we report that a Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. occupancies led to elevated MLL1 recruitment aberrant homeotic topologically associated domains (TADs) enhanced accessibilities homeotic/hematopoietic oncogenes. HoxBlinc-depletion NUP98...
A distinct population of therapy-related acute myeloid leukemia (t-AML) is strongly associated with prior administration topoisomerase II (topo II) inhibitors. These t-AMLs display cytogenetic alterations, most often disrupting the MLL gene on chromosome 11q23 within a breakpoint cluster region (bcr) 8.3 kb. We recently identified unique site bcr that highly susceptible to DNA double-strand cleavage by classic topo inhibitors (e.g., etoposide and doxorubicin). Here, we report site-specific...
The receptors for transforming growth factor beta (TGF-beta) and their signaling intermediates make up an important tumor-suppressor pathway. role of one these intermediates--Smad3--in the pathogenesis lymphoid neoplasia is unknown.We measured Smad3 messenger RNA (mRNA) protein in leukemia cells obtained at diagnosis from 19 children with acute leukemia, including 10 T-cell lymphoblastic (ALL), 7 pre-B-cell ALL, 2 nonlymphoblastic (ANLL). All nine exons SMAD3 gene (MADH3) were sequenced....
Deciphering molecular events required for full transformation of normal cells into cancer remains a challenge. In T-cell acute lymphoblastic leukemia (T-ALL), the genes encoding TAL1/SCL and LMO1/2 transcription factors are recurring targets chromosomal translocations, whereas NOTCH1 is activated in >50% samples. Here we show that SCL LMO1 oncogenes collaborate to expand primitive thymocyte progenitors inhibit later stages differentiation. Together with pre-T-cell antigen receptor...
Abstract Although HMGA1 (high-mobility group A1; formerly HMG-I/Y) is an oncogene that widely overexpressed in aggressive cancers, the molecular mechanisms underlying transformation by are only beginning to emerge. encodes HMGA1a and HMGA1b protein isoforms, which function regulating gene expression. To determine how leads neoplastic transformation, we looked for genes regulated using expression profile analysis. Here, show STAT3 gene, signaling molecule signal transducer activator of...
Epigenetic silencing plays an important role in cancer development. An attractive hypothesis is that local DNA features may participate differential predisposition to gene hypermethylation. We found that, compared with methylation-resistant genes, methylation-prone genes have a lower frequency of SINE and LINE retrotransposons near their transcription start site. In several large testing sets, this distribution was highly predictive promoter methylation. Genome-wide analysis showed 22% human...