Complex chromosomal abnormalities in utero, 5 years before leukaemia.
Prenatal acquisition of leukaemia-associated gene rearrangements is a well-established phenomenon. This is the first report of a complex cytogenetic clone, in association with an ETV6/AML1 fusion, developing in utero. Identical twin girls, aged 4 years, developed ETV6/AML1-positive acute lymphoblastic leukaemia (ALL) within 3 months of one another. Both demonstrated an identical four way, variant t(12;21). There was gain of an AML1 signal in twin 1 and loss of an ETV6 one in twin 2 at interphase. This unique case study demonstrates that ETV6/AML1 fusion and the associated complex chromosomal rearrangements occurred in utero. Clonal expansion of the abnormal cell in one twin was followed by metastasis to the other. There was a prolonged preleukaemic phase, which lasted well into childhood. The short time between the two diagnoses of ALL suggests a common precipitating event. The significance of the different secondary markers remains unclear.
Broadfield
Zoë J
ZJ
Leukaemia Research Fund Cytogenetics Group, Cancer Sciences Division, University of Southampton, Southampton, UK. zjb@soton.ac.uk
Hain
Richard D W
RD
Harrison
Christine J
CJ
Reza Jalali
G
G
McKinley
Mark
M
Michalová
Kyra
K
Robinson
Hazel M
HM
Zemanová
Zuzana
Z
Martineau
Mary
M
D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D002999:Clone Cells; D050676:Core Binding Factor Alpha 2 Subunit; D004200:Diseases in Twins / Q000196:embryology* / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000196:embryology* / Q000235:genetics*; D011289:Preleukemia / Q000196:embryology / Q000235:genetics; D014178:Translocation, Genetic; D014430:Twins, Monozygotic; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein