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Complex chromosomal abnormalities in utero, 5 years before leukaemia
Zoë J Broadfield1, Richard D W Hain, Christine J Harrison
1Leukaemia Research Fund Cytogenetics Group, Cancer Sciences Division, University of Southampton, Southampton, UK. zjb@soton.ac.uk
British Journal of Haematology
|July 20, 2004
Summary
This study reports the first case of in utero development of ETV6/AML1-positive acute lymphoblastic leukemia (ALL) in identical twins. The findings suggest prenatal gene rearrangement and metastasis between twins, with a prolonged preleukaemic phase.
Area of Science:
- Pediatric Oncology
- Cancer Genetics
- Hematology
Background:
- Prenatal acquisition of gene rearrangements linked to leukemia is known.
- ETV6/AML1 fusion is a common genetic alteration in childhood acute lymphoblastic leukemia (ALL).
Purpose of the Study:
- To report the first case of a complex cytogenetic clone with ETV6/AML1 fusion developing in utero.
- To investigate the prenatal origin and transmission of leukemia in identical twins.
Main Methods:
- Karyotyping and interphase fluorescence in situ hybridization (FISH) were used.
- Analysis of identical twin girls diagnosed with ALL.
Main Results:
- Identical twin girls developed ETV6/AML1-positive ALL within months of each other.
- Both twins shared an identical four-way variant t(12;21) chromosomal rearrangement.
- Evidence suggests prenatal development, clonal expansion, and metastasis between twins.
- A prolonged preleukaemic phase was observed in both children.
Conclusions:
- The ETV6/AML1 fusion and complex chromosomal rearrangements likely occurred in utero.
- Metastasis of abnormal cells from one twin to the other is a plausible transmission route.
- The findings highlight the potential for prenatal oncogenesis and a long preleukaemic phase in childhood ALL.