Linked Life Data

11986236

Source:http://linkedlifedata.com/resource/pubmed/id/11986236

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2002-5-2
pubmed:abstractText
The t(10;11)(p12;q23) chromosomal translocation in human acute myeloid leukemia results in the fusion of the MLL and AF10 genes. The latter codes for a novel leucine zipper protein, one of many MLL fusion partners of unknown function. In this report, we demonstrate that retroviral-mediated transduction of an MLL-AF10 complementary DNA into primary murine myeloid progenitors enhanced their clonogenic potential in serial replating assays and led to their efficient immortalization at a primitive stage of myeloid differentiation. Furthermore, MLL-AF10-transduced cells rapidly induced acute myeloid leukemia in syngeneic or severe combined immunodeficiency recipient mice. Structure/function analysis showed that a highly conserved 82-amino acid portion of AF10, comprising 2 adjacent alpha-helical domains, was sufficient for immortalizing activity when fused to MLL. Neither helical domain alone mediated immortalization, and deletion of the 29-amino acid leucine zipper within this region completely abrogated transforming activity. Similarly, the minimal oncogenic domain of AF10 exhibited transcriptional activation properties when fused to the MLL or GAL4 DNA-binding domains, while neither helical domain alone did. However, transcriptional activation per se was not sufficient because a second activation domain of AF10 was neither required nor competent for transformation. The requirement for alpha-helical transcriptional effector domains is similar to the oncogenic contributions of unrelated MLL partners ENL and ELL, suggesting a general mechanism of myeloid leukemogenesis by a subset of MLL fusion proteins, possibly through specific recruitment of the transcriptional machinery.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3780-5
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11986236-Amino Acid Motifs, pubmed-meshheading:11986236-Amino Acid Sequence, pubmed-meshheading:11986236-Animals, pubmed-meshheading:11986236-COS Cells, pubmed-meshheading:11986236-Cell Line, pubmed-meshheading:11986236-Cell Transformation, Neoplastic, pubmed-meshheading:11986236-Cells, Cultured, pubmed-meshheading:11986236-Conserved Sequence, pubmed-meshheading:11986236-DNA-Binding Proteins, pubmed-meshheading:11986236-Leucine Zippers, pubmed-meshheading:11986236-Leukemia, Myeloid, pubmed-meshheading:11986236-Mice, pubmed-meshheading:11986236-Mice, Inbred C57BL, pubmed-meshheading:11986236-Mice, SCID, pubmed-meshheading:11986236-Molecular Sequence Data, pubmed-meshheading:11986236-Myeloid Progenitor Cells, pubmed-meshheading:11986236-Myeloid-Lymphoid Leukemia Protein, pubmed-meshheading:11986236-Oncogene Proteins, Fusion, pubmed-meshheading:11986236-Protein Structure, Tertiary, pubmed-meshheading:11986236-Proto-Oncogenes, pubmed-meshheading:11986236-Sequence Alignment, pubmed-meshheading:11986236-Transcription Factors, pubmed-meshheading:11986236-Transcriptional Activation, pubmed-meshheading:11986236-Transduction, Genetic
pubmed:year
2002
pubmed:articleTitle
The AF10 leucine zipper is required for leukemic transformation of myeloid progenitors by MLL-AF10.
pubmed:affiliation
Department of Pathology, Stanford University School of Medicine, CA 94305, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.