Linked Life Data

16044150

Source:http://linkedlifedata.com/resource/pubmed/id/16044150

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
2005-11-18
pubmed:abstractText
The t(12;21) translocation, generating the TEL/AML1 fusion protein, is the most common genetic lesion in childhood cancer. Using a bone marrow transplantation model, we demonstrate that TEL/AML1 expression impinges on normal hematopoietic differentiation, leading to the in vivo accumulation and persistence of an early progenitor compartment with a Sca1(+)/Kit(hi)/CD11b(+) phenotype and an increased self-renewal capacity, as documented by replating assays in vitro. Differentiation of these cells is not blocked, but the frequency of mature blood cells arising from TEL/AML1-transduced progenitors is low. Impaired differentiation is prominently observed in the pro-B-cell compartment, resulting in an proportional increase in early progenitors in vivo, consistent with the t(12;21) ALL phenotype. Despite the accumulation of both multipotent and B-cell progenitors in vivo, no leukemia induction was observed during an observation period of over 1 year. These results are consistent with findings in twins with concordant ALL, showing that TEL/AML1 generates a preleukemic clone in utero that persists for several years in a clinically covert fashion. Furthermore, our studies showed that the pointed domain of TEL/AML1, which recruits transcriptional repressors and directs oligomerization with either TEL/AML1 or wild-type TEL, was essential for the observed differentiation impairment and could not be replaced with another oligomerization domain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7579-91
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16044150-Animals, pubmed-meshheading:16044150-B-Lymphocytes, pubmed-meshheading:16044150-Bone Marrow Transplantation, pubmed-meshheading:16044150-Cell Differentiation, pubmed-meshheading:16044150-Cell Transformation, Neoplastic, pubmed-meshheading:16044150-Chromosomes, Human, Pair 12, pubmed-meshheading:16044150-Chromosomes, Human, Pair 21, pubmed-meshheading:16044150-Core Binding Factor Alpha 2 Subunit, pubmed-meshheading:16044150-Hematopoietic Stem Cells, pubmed-meshheading:16044150-Humans, pubmed-meshheading:16044150-Mice, pubmed-meshheading:16044150-Mice, Inbred C57BL, pubmed-meshheading:16044150-Oncogene Proteins, Fusion, pubmed-meshheading:16044150-Phenotype, pubmed-meshheading:16044150-Precursor Cell Lymphoblastic Leukemia-Lymphoma, pubmed-meshheading:16044150-Preleukemia, pubmed-meshheading:16044150-Translocation, Genetic
pubmed:year
2005
pubmed:articleTitle
Defining the oncogenic function of the TEL/AML1 (ETV6/RUNX1) fusion protein in a mouse model.
pubmed:affiliation
Molecular Pathology Group, Heinrich-Pette-Institut für Experimentelle Immunologie und Virologie, D-20251 Hamburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't