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Pre-natal, clonal origin of t(1;11)(p32;q23) acute lymphoblastic leukemia in monozygotic twins.
MedLine Citation:
PMID:  21474181     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIM: Observation of identical genetic changes in leukemia cells from monozygotic twin pairs has provided evidence for the in utero single clonal origin hypothesis of leukemia, with intraplacental metastasis the basis for concordance. Investigation of this rare mixed lineage leukemia (MLL) cytogenetic abnormality aims to provide further evidence of the genetic changes that underpin this aggressive form of leukemia in infants. METHOD: The clinical features of a monozygotic infant twin pair with acute lymphoblastic leukemia (ALL) are reported. Banded chromosomal analysis and fluorescent in situ hybridization were used for cytogenetic characterization of the leukemic cells. Immunophenotype was determined by flow cytometry and polymerase chain reaction was used to determine the presence of FLT3-D835/I836 and FLT3-internal tandem duplication (ITD) mutations. RESULTS: The twins were seven weeks of age at diagnosis. Both had cytogenetic evidence for the t(1;11)(p32;q23) translocation. Trisomy X was present in a subpopulation of cells in one twin. Immunophenotypic profile at diagnosis was consistent with B precursor ALL (CD19, CD24, CD33 positive, weak CD13 positivity, CD10 negative) and both were negative for FLT3-D835/I836 and FLT3-ITD mutations. CONCLUSIONS: This is the first report of monochorionic monozygotic twins harboring the t(1;11)(p32;q23) translocation. Identification of this rare translocation in both twins, indicates a common stem line and provides further evidence for the intrauterine monoclonal origin for infant ALL with concordance explained by the shared circulation. Genetic diversity was observed in a subpopulation of cells from one twin at diagnosis. We must now utilize the sophisticated molecular biology tools available to capture changes at the genome-wide level to gain further insight into the complex events contributing to MLL leukemogenesis in infants.
Authors:
Rishi S Kotecha; Ashleigh Murch; Ursula Kees; Catherine H Cole
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-5
Journal Detail:
Title:  Leukemia research     Volume:  -     ISSN:  1873-5835     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7706787     Medline TA:  Leuk Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.
Affiliation:
Department of Hematology and Oncology, Princess Margaret Hospital for Children, Perth, WA, Australia; Telethon Institute for Child Health Research and Center for Child Health Research, University of Western Australia, Perth, WA, Australia; School of Pediatrics and Child Health, University of Western Australia, Perth, WA, Australia.
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