Linked Life Data

19023877

Source:http://linkedlifedata.com/resource/pubmed/id/19023877

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-1-12
pubmed:abstractText
The translocation t(16;21) involving RUNX1 (AML1) and resulting in the RUNX1-CBFA2T3 fusion is a rare but recurrent abnormality mostly found in therapy-related acute myeloid leukemia (t-AML) associated with agents targeting topoisomerase II (topo II). We characterized, at the genomic level, the t(16;21) translocation in a patient who developed t-AML after treatment of multiple sclerosis with mitoxantrone (MTZ). Long template nested PCR of genomic DNA followed by direct sequencing enabled the localization of RUNX1 and CBFA2T3 (ETO2) breakpoints in introns 5 and 3, respectively. Sequencing of the cDNA with specific primers showed the presence of the expected RUNX1-CBFA2T3 fusion transcript in leukemic cells. The RUNX1 intron 5 breakpoint was located at nucleotide position 24,785. This region contained an ATGCCCCAG nucleotide sequence showing approximately 90% homology to a "hotspot" DNA region ATGCCCTAG present in intron 6 of PML previously identified in therapy-related acute promyelocytic leukemia cases arising following treatment with MTZ. This study suggests a wider distribution in the human genome, and particularly at genes involved in chromosome translocations observed in t-AML, of DNA regions (hotspot) targeted by specific topo II drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1098-2264
pubmed:author
pubmed:copyrightInfo
Copyright 2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
213-21
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19023877-Core Binding Factor Alpha 2 Subunit, pubmed-meshheading:19023877-Cytogenetic Analysis, pubmed-meshheading:19023877-Databases, Genetic, pubmed-meshheading:19023877-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19023877-Humans, pubmed-meshheading:19023877-In Situ Hybridization, Fluorescence, pubmed-meshheading:19023877-Leukemia, Myeloid, Acute, pubmed-meshheading:19023877-Male, pubmed-meshheading:19023877-Middle Aged, pubmed-meshheading:19023877-Mitoxantrone, pubmed-meshheading:19023877-Multiple Sclerosis, pubmed-meshheading:19023877-Oncogene Proteins, Fusion, pubmed-meshheading:19023877-Phosphoproteins, pubmed-meshheading:19023877-Repressor Proteins, pubmed-meshheading:19023877-Sequence Analysis, DNA, pubmed-meshheading:19023877-Topoisomerase II Inhibitors, pubmed-meshheading:19023877-Translocation, Genetic, pubmed-meshheading:19023877-Tumor Suppressor Proteins
pubmed:year
2009
pubmed:articleTitle
Identification of a potential "hotspot" DNA region in the RUNX1 gene targeted by mitoxantrone in therapy-related acute myeloid leukemia with t(16;21) translocation.
pubmed:affiliation
Dipartimento di Biopatologia e Diagnostica per Immagini, University Tor Vergata, Rome, Italy.
pubmed:publicationType
Journal Article, Case Reports, Research Support, Non-U.S. Gov't