Genetic lesions in a preleukemic aplasia phase in a child with acute lymphoblastic leukemia.
Genes Chromosomes Cancer
; 47(4): 333-40, 2008 Apr.
Article
em En
| MEDLINE
| ID: mdl-18181181
ABSTRACT
In a small fraction ( approximately 2%) of cases of childhood acute lymphoblastic leukemia (ALL) clinical presentation of leukemia is preceded, some 2-9 months earlier, by a transient, remitting phase of nonclassical aplastic anemia, usually in connection with infection. The potential "preleukemic" nature of this prodromal phase has not been fully explored. We have retrospectively analyzed the blood and bone marrow of a child who presented with aplastic anemia 9 months before the development of ETV6-RUNX1 fusion gene positive ALL. High resolution SNP genotyping arrays identified 11 regions of loss of heterozygosity, with and without concurrent copy number changes, at the presentation of ALL. In all cases of copy number change, the deletion or gain identified by single nucleotide polymorphism (SNP) analysis was confirmed in the ALL blasts by FISH. Retrospective analysis of aplastic phase bone marrow showed that the ETV6-RUNX1 fusion was present along with all of the additional genetic changes assessed, albeit subclonal to ETV6-RUNX1. These data identify for the first time the leukemic genotype of an aplasia preceding clinical ALL and indicate that multiple secondary genetic abnormalities can contribute to a dominant subclone several months before a diagnosis of ALL. These data have implications for the biology of ALL and for management of similar patients.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pré-Leucemia
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Proteínas de Fusão Oncogênica
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Subunidade alfa 2 de Fator de Ligação ao Core
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Anemia Aplástica
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Child, preschool
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Humans
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Male
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article