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rdf:type |
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lifeskim:mentions |
umls-concept:C0004083,
umls-concept:C0008633,
umls-concept:C0012854,
umls-concept:C0023487,
umls-concept:C0162326,
umls-concept:C0205369,
umls-concept:C0936012,
umls-concept:C1366536,
umls-concept:C1366903,
umls-concept:C1514562,
umls-concept:C1515568,
umls-concept:C1708726,
umls-concept:C1721104
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pubmed:issue |
8
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pubmed:dateCreated |
2010-6-14
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pubmed:abstractText |
We compared genomic breakpoints at the PML and RARA loci in 23 patients with therapy-related acute promyelocytic leukemia (t-APL) and 25 de novo APL cases.Eighteen of 23 t-APL cases received the topoisomerase II poison mitoxantrone for their primary disorder. DNA breaks were clustered in a previously reported 8 bp "hot spot" region of PML corresponding to a preferred site of mitoxantrone-induced DNA topoisomerase II-mediated cleavage in 39% of t-APL occurring in patients exposed to this agent and in none of the cases arising de novo (P = 0.007). As to RARA breakpoints, clustering in a 3' region of intron 2 (region B) was found in 65% of t-APL and 28% of de novo APL patients, respectively. Scan statistics revealed significant clustering of RARA breakpoints in region B in t-APL cases (P = 0.001) as compared to de novo APL (P = 1). Furthermore, approximately 300 bp downstream of RARA region B contained a sequence highly homologous to a topoisomerase II consensus sequence. Biased distribution of DNA breakpoints at both PML and RARA loci suggest the existence of different pathogenetic mechanisms in t-APL as compared with de novo APL.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Mitoxantrone,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PML protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/retinoic acid receptor alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1098-2264
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pubmed:author |
pubmed-author:AmadoriSergioS,
pubmed-author:BernasconiPaoloP,
pubmed-author:DöhnerHartmutH,
pubmed-author:Di RaimondoFrancescoF,
pubmed-author:GrimwadeDavidD,
pubmed-author:HasanSyed KhizerSK,
pubmed-author:Lo-CocoFrancescoF,
pubmed-author:MarcoPepaP,
pubmed-author:MaysAshley NAN,
pubmed-author:MitraMaria EnzaME,
pubmed-author:OttoneTizianaT,
pubmed-author:SanzMiguel AMA,
pubmed-author:SchlenkRichard FRF,
pubmed-author:StanghelliniMaria Teresa LupoMT,
pubmed-author:WiemelsJoseph LJL,
pubmed-author:XiaoYuanyuanY
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pubmed:issnType |
Electronic
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pubmed:volume |
49
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
726-32
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pubmed:meshHeading |
pubmed-meshheading:20544846-Adult,
pubmed-meshheading:20544846-Aged,
pubmed-meshheading:20544846-Antineoplastic Agents,
pubmed-meshheading:20544846-Chromosome Breakpoints,
pubmed-meshheading:20544846-Chromosomes, Human, Pair 15,
pubmed-meshheading:20544846-Chromosomes, Human, Pair 17,
pubmed-meshheading:20544846-DNA, Neoplasm,
pubmed-meshheading:20544846-Female,
pubmed-meshheading:20544846-Humans,
pubmed-meshheading:20544846-Leukemia, Promyelocytic, Acute,
pubmed-meshheading:20544846-Male,
pubmed-meshheading:20544846-Middle Aged,
pubmed-meshheading:20544846-Mitoxantrone,
pubmed-meshheading:20544846-Nuclear Proteins,
pubmed-meshheading:20544846-RNA, Messenger,
pubmed-meshheading:20544846-Receptors, Retinoic Acid,
pubmed-meshheading:20544846-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20544846-Transcription Factors,
pubmed-meshheading:20544846-Translocation, Genetic,
pubmed-meshheading:20544846-Tumor Suppressor Proteins,
pubmed-meshheading:20544846-Young Adult
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pubmed:year |
2010
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pubmed:articleTitle |
Analysis of t(15;17) chromosomal breakpoint sequences in therapy-related versus de novo acute promyelocytic leukemia: association of DNA breaks with specific DNA motifs at PML and RARA loci.
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pubmed:affiliation |
Department of Biopathology, University of 'Rome Tor Vergata', Rome, Italy. syedk.hasan@uniroma2.it
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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