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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
1992-5-6
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pubmed:abstractText |
The characteristic t(15;17) of acute promyelocytic leukemia (APL) fuses the retinoic acid receptor alpha (RAR-alpha) gene on chromosome 17 to a gene on chromosome 15 called PML, a putative transcription factor. This distinct translocation results in a fusion mRNA detected by Northern analysis. Two cDNAs have been isolated that differ in the extent of 3' PML nucleic acid sequence contained. This study describes a reverse transcription polymerase chain reaction (RT-PCR) assay for the PML/RAR-alpha fusion transcript, which amplifies PML/RAR-alpha mRNA from APL cells with either reported breakpoint. DNA sequencing of the predominant RT-PCR products from 6 patients showed identical RAR-alpha exonic breakpoints and two PML breakpoints. This RT-PCR assay was positive in leukemic cells from 30/30 APL patients with the molecular rearrangement confirmed by cytogenetics or Northern analysis. In leukemic cells of patients with a morphologic diagnosis of APL lacking the t(15;17) by routine cytogenetics, a positive RT-PCR assay predicted clinical response to all-trans-retinoic acid (RA) therapy. Dilutional studies with leukemic cells that express (NB4) or do not express (HL-60) a PML/RAR-alpha fusion mRNA reveal that this RT-PCR assay detects the transcript from as little as 50 pg of total RNA. In APL cells from 5/6 patients treated with RA alone, a complete response by clinical and cytogenetic criteria accompanied a persistently positive RT-PCR assay. This preceded relapse by 1-6 months. RT-PCR for PML/RAR-alpha mRNA provides a more-sensitive test for the t(15;17) than routine cytogenetics or Northern analysis. This molecular rearrangement detected by RT-PCR best defines this RA-responsive malignancy. The RT-PCR assay for the PML/RAR-alpha transcript yields important diagnostic and prognostic information in the management of APL patients.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-1195397,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-1650447,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-1652368,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-1652369,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-1848017,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-1849030,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-1850498,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-1884013,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-1993225,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-1995093,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-2170850,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-2173802,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-2174466,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-2175343,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-2189506,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-2224119,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-2237408,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-2349080,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-271968,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-2825025,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-2825036,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-3165197,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-3165295,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-3194208,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-3422031,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-3455866,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-3862359,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-518835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/1372989-6586073
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
89
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2694-8
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pubmed:dateRevised |
2010-9-7
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pubmed:meshHeading |
pubmed-meshheading:1372989-Base Sequence,
pubmed-meshheading:1372989-Blotting, Northern,
pubmed-meshheading:1372989-Carrier Proteins,
pubmed-meshheading:1372989-Chromosome Aberrations,
pubmed-meshheading:1372989-Chromosome Disorders,
pubmed-meshheading:1372989-Gene Expression,
pubmed-meshheading:1372989-Gene Rearrangement,
pubmed-meshheading:1372989-Humans,
pubmed-meshheading:1372989-Leukemia, Promyelocytic, Acute,
pubmed-meshheading:1372989-Molecular Sequence Data,
pubmed-meshheading:1372989-Oligodeoxyribonucleotides,
pubmed-meshheading:1372989-Polymerase Chain Reaction,
pubmed-meshheading:1372989-Prognosis,
pubmed-meshheading:1372989-RNA, Messenger,
pubmed-meshheading:1372989-RNA-Directed DNA Polymerase,
pubmed-meshheading:1372989-Receptors, Retinoic Acid,
pubmed-meshheading:1372989-Translocation, Genetic,
pubmed-meshheading:1372989-Tretinoin
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pubmed:year |
1992
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pubmed:articleTitle |
Reverse transcription polymerase chain reaction for the rearranged retinoic acid receptor alpha clarifies diagnosis and detects minimal residual disease in acute promyelocytic leukemia.
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pubmed:affiliation |
Laboratory of Molecular Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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