Document Detail


PML/RARalpha, a fusion protein in acute promyelocytic leukemia, prevents growth factor withdrawal-induced apoptosis in TF-1 cells.
MedLine Citation:
PMID:  9816019     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A unique mRNA produced by the t(15;17) (q22-24;q11-21) translocation in the leukemic cells of acute promyelocytic leukemia patients encodes a chimeric protein, PML/RARalpha, which is formed by the fusion of the retinoic acid receptor alpha (RARalpha) and the promyelocytic locus gene (PML). This translocation is often the only visible karyotypic aberration present which is detected in almost 100% of acute promyelocytic leukemia patients. As an initial step to study the role of PML/RARalpha in leukemogenesis, we attempted to express the fusion protein in hematopoietic cells through retrovirus-mediated gene transfer of the retroviral vector, pGPRCHT, which contains the PML/RARalpha cDNA. Transduction of the PML/RARalpha cDNA fragment used in this vector, which extends from the position 31 bp to the position 2638 bp in a transcription unit driven by the Moloney murine sarcoma virus LTR, was found to abrogate the growth factor dependence of TF-1 cells. In addition, introduction of PML/RARalpha into TF-1 cells can protect these cells from the apoptosis usually induced in TF-1 cells by growth factor withdrawal, as measured by three assays for apoptosis: morphology, DNA ladder formation, and end labeling of nicked DNA with fluorescent-conjugated nucleotide precursors followed by a fluorescence-activated cell sorting assay. These data suggest that the PML/RARalpha fusion protein may inhibit programmed cell death in myeloid cells.
Authors:
S Fu; U Consoli; E G Hanania; Z Zu; D F Claxton; M Andreeff; A B Deisseroth
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  1     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  1995 Jun 
Date Detail:
Created Date:  1999-02-08     Completed Date:  1999-02-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  583-90     Citation Subset:  IM    
Affiliation:
Department of Hematology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / physiology*
Cell Division / drug effects
Chromosome Mapping
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 17
Genetic Vectors
Growth Substances / pharmacology,  physiology
Humans
Leukemia, Promyelocytic, Acute / genetics*
Models, Biological
Neoplasm Proteins / genetics*,  metabolism*
Oncogene Proteins, Fusion / genetics*,  metabolism*
Recombinant Fusion Proteins / metabolism
Retroviridae
Reverse Transcriptase Polymerase Chain Reaction
Transfection
Translocation, Genetic
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
CA16672/CA/NCI NIH HHS; CA57639/CA/NCI NIH HHS; P01 CA55164/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Growth Substances; 0/Neoplasm Proteins; 0/Oncogene Proteins, Fusion; 0/Recombinant Fusion Proteins; 0/promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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