Linked Life Data

12562214

Source:http://linkedlifedata.com/resource/pubmed/id/12562214

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-2-3
pubmed:abstractText
The best studied T cell leukemia/lymphoma from a genetic and biochemical point of view is T-cell chronic lymphocytic/prolymphocytic leukemia (T-CLL/T-PLL). This neoplasia commonly shows chromosomal rearrangements at 14q32.1 including translocations [t(14;14)(q11;q32), t(7;14)(q35;q32)], and inversions [inv(14)(q11;q32)]. The investigation of the locus in question at 14q32.1 resulted in the identification of two related genes named T cell leukemia/lymphoma 1 (TCL1) and TCL1b. Both genes are activated in T-CLL/T-PLL by the chromosomal aberrations mentioned above. Mice from a transgenic mouse strain expressing the TCL1 gene under the thymocyte specific lck promoter developed a mature T cell leukemia late in life, thereby demonstrating that over-expression of TCL1 induces the neoplastic transformation of T cells. Biochemically, Tcl1 protein works as a co-factor of the Akt kinase, a key regulator of antiapoptotic and proliferative signals. Tcl1 interacts physically with Akt, increases its kinase activity and facilitates its transport to the nucleus. The pathogenesis of T-CLL/T-PLL may also involve Nur77, a T cell transcription factor required for T cell receptor-mediated apoptosis. Akt phosphorylates Nur77, thereby blocking its DNA-binding ability and rendering the transcription factor inactive. The recently emerged insights into the molecular mechanisms of T cell leukemogenesis will allow for the development of specific pharmacological tools for the treatment of these hematopoietic malignancies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:issn
1175-2203
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Targeting mature T cell leukemia: new understanding of molecular pathways.
pubmed:affiliation
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. Y_Pekarsky@lac.jci.tju.edu
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't