Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-1-19
pubmed:abstractText
Oncoprotein E2a/Pbx1 is produced by the t(1;19) chromosomal translocation of human pre-B acute lymphoblastic leukemia. E2a/Pbx1 blocks differentiation of primary myeloid progenitors but, paradoxically, induces apoptosis in established pre-B-cell lines, and no transforming function of E2a/Pbx1 has been reported in cultured lymphoid progenitors. Here, we demonstrate that E2a/Pbx1 induces immortal proliferation of stem cell factor (SCF)-dependent pro-T thymocytes by a mechanism dependent upon both its transactivation and DNA-binding functions. E2a-Pbx1 cooperated with cytokines or activated signaling oncoproteins to induce cell division, as inactivation of conditional E2a/Pbx1 in either factor-dependent pro-T cells or pro-T cells made factor independent by expression of Bcr/Abl resulted in pro-T-cell quiescence, while reactivation of E2a/Pbx1 restored cell division. Infusion of E2a/Pbx1 pro-T cells in mice caused T lymphoblastic leukemia and, unexpectedly, acute myeloid leukemia. The acute lymphoblastic leukemia did not evidence further maturation, suggesting that E2a/Pbx1 establishes an early block in pro-T-cell development that cannot be overcome by marrow or thymic microenvironments. In an E2a/Pbx1 pro-T thymocyte clone that induced only pro-T acute lymphoblastic leukemia, coexpression of Bcr/Abl expanded its leukemic phenotype to include acute myeloid leukemia, suggesting that unique functions of cooperating signaling oncoproteins can influence the lymphoid versus myeloid character of E2a/Pbx1 leukemia and may cooperate with E2a/Pbx1 to dictate the pre-B-cell phenotype of human leukemia containing t(1;19).
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-10330184, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-10367900, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-10373552, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-10374871, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-10452996, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-10514008, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-10602420, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-10637514, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-10724173, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-10913162, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-10933396, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11014194, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11248806, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11296270, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11420675, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11490000, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11560990, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11561160, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11588024, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11687616, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11840323, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11895769, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11900454, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11910894, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-11917122, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-12082612, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-12916872, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-1382094, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-1862078, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-1989880, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-6607758, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-7584069, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-7600286, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-7734349, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-7873385, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-7923373, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-7926766, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-7936638, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-7964471, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-7969166, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-7995521, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-8093327, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-8104101, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-8387091, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-8552391, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-8605871, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-8945476, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-9234734, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-9393859, http://linkedlifedata.com/resource/pubmed/commentcorrection/14729970-9808576
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Lymphoid Enhancer-Binding Factor 1, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Pbx1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Notch, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Stem Cell Factor, http://linkedlifedata.com/resource/pubmed/chemical/Tle1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/pbx1 protein, human
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0270-7306
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1256-69
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
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