Linked Life Data

9778041

Source:http://linkedlifedata.com/resource/pubmed/id/9778041

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1998-11-25
pubmed:abstractText
The t(15;17) rearrangement found in acute promyelocytic leukemia (APL) yields a fusion transcript, PML/RAR alpha. PML/RAR alpha expression is linked to leukemogenesis and to clinical sensitivity to all-trans retinoic acid (RA). Paradoxically, RA treatment causes transient complete remissions in most t(15;17) APL cases. The precise roles of PML/RAR alpha in triggering leukemia or in causing a maturation block are not yet known. This study explores directly these PML/RAR alpha functions in the growth and differentiation of APL cells using a hammerhead ribozyme to target PML/RAR alpha mRNA in the NB4 APL cell line. When the PML/RAR alpha cleaving but not the non-catalytic control ribozyme is introduced into the NB4 APL cell line, PML/RAR alpha protein expression is reduced. This catalysis signals growth suppression, cytotoxicity, and apoptosis without overcoming the maturation block found in these leukemic cells. These biologic effects depend on the selective pressure used to express the ribozyme from an episomal vector. Introduction of a non-catalytic, control ribozyme into NB4 cells caused no observed phenotype due to anti-sense activities. Expression of the catalytic or non-catalytic ribozymes in control cells lacking PML/RAR alpha mRNA yielded no apparent growth or differentiation effects. Thus, use of a hammerhead ribozyme that targets PML/RAR alpha expression in APL cells reveals the anti-apoptotic function of this translocation product and demonstrates that PML/RAR alpha cleavage is insufficient to overcome the differentiation block observed in these leukemic cells. Taken together, these findings indicate that persistent PML/RAR alpha expression is required to maintain basal leukemic cell growth and point to the therapeutic potential of targeting PML/RAR alpha in APL.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1759-68
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Targeting the PML/RAR alpha translocation product triggers apoptosis in promyelocytic leukemia cells.
pubmed:affiliation
Department of Medicine, Memorial Hospital, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't