Prenatal chromosomal diversification of leukemia in monozygotic twins.
Previous studies on concordant acute lymphoblastic leukemia (ALL) in identical twins have identified the leukemia as monoclonal with MLL or ETV6-RUNX1 gene fusion as early or initiating events in utero. In the latter case, postnatal latency is associated with secondary genetic events such as ETV6 deletion. We describe here a pair of infant twins with concordant acute monoblastic leukemia (AML). They are a unique pair in that their leukemia blasts display extensive intraclonal chromosomal diversity. Comparison of the leukemic cells between the two twins by karyotype and fluorescence in situ hybridization identifies a common or shared stem line and extensive subclonal diversity for which the twins' leukemic populations are divergent. This case of leukemia illustrates in utero initiation with early imposition of chromosomal instability, the progressively divergent evolution of which can be mapped in the twins into pre- and postnatal periods.
Kempski
Helena
H
Molecular Haematology Unit, Institute of Child Health, London, United Kingdom. H.Kempski@ich.ucl.ac.uk
Mensa-Bonsu
Karen A
KA
Kearney
Lyndal
L
Jalali
G Reza
GR
Hann
Ian
I
Khurshid
Mohammed
M
Greaves
Mel
M
D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics; D004200:Diseases in Twins / Q000196:embryology* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007948:Leukemia, Monocytic, Acute / Q000196:embryology* / Q000235:genetics*; D008297:Male; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
D004268:DNA-Binding Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein