Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2009-2-20
pubmed:abstractText
Understanding the pathways that regulate the human T-cell acute lymphoblastic leukemia (T-ALL) initiating cells (T-LiC) activity has been hampered by the lack of biologic assays in which this human disease can be studied. Here we show that coculture of primary human T-ALL with a mouse stromal cell line expressing the NOTCH ligand delta-like-1 (DL1) reproducibly allowed maintenance of T-LiC and long-term growth of blast cells. Human T-ALL mutated or not on the NOTCH receptor required sustained activation of the NOTCH pathway via receptor/ligand interaction for growth and T-LiC activity. On the reverse, inhibition of the NOTCH pathway during primary cultures abolished in vitro cell growth and in vivo T-LiC activity. Altogether, these results demonstrate the major role of the NOTCH pathway activation in human T-ALL development and in the maintenance of leukemia-initiating cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1730-40
pubmed:dateRevised
2009-6-26
pubmed:meshHeading
pubmed-meshheading:18984862-Amyloid Precursor Protein Secretases, pubmed-meshheading:18984862-Animals, pubmed-meshheading:18984862-Cell Communication, pubmed-meshheading:18984862-Cell Culture Techniques, pubmed-meshheading:18984862-Coculture Techniques, pubmed-meshheading:18984862-Genes, T-Cell Receptor gamma, pubmed-meshheading:18984862-Humans, pubmed-meshheading:18984862-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:18984862-Membrane Proteins, pubmed-meshheading:18984862-Mice, pubmed-meshheading:18984862-Mice, Inbred NOD, pubmed-meshheading:18984862-Mice, SCID, pubmed-meshheading:18984862-Neoplasm Transplantation, pubmed-meshheading:18984862-Oligopeptides, pubmed-meshheading:18984862-Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, pubmed-meshheading:18984862-Receptor, Notch1, pubmed-meshheading:18984862-Signal Transduction, pubmed-meshheading:18984862-Stromal Cells, pubmed-meshheading:18984862-Tumor Cells, Cultured
pubmed:year
2009
pubmed:articleTitle
NOTCH is a key regulator of human T-cell acute leukemia initiating cell activity.
pubmed:affiliation
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 8104 Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't