Covert preleukemia driven by MLL gene fusion.
Genes Chromosomes Cancer
; 48(1): 98-107, 2009 Jan.
Article
em En
| MEDLINE
| ID: mdl-18932267
ABSTRACT
Acute leukemia is considered to be a two- or multiple-step process. Although there is a considerable knowledge regarding the character of the "first hit," the nature of the "second hit" remains unanswered in most of the cases including leukemias with MLL gene rearrangement. We demonstrate here a striking sequence of events, which include a covert, protracted preleukemic phase characterized by a dominant MLL/FOXO3A clone with intact myeloid differentiation and the subsequent acquisition of a secondary genetic abnormality, leading to overt lymphoblastic leukemia. Backtracking of the secondary acute lymphoblastic leukemia (sALL) with the MLL rearrangement showed no blasts in the bone marrow (BM) during the protracted preleukemic phase. However, at the same time (more than 1 year before the sALL diagnosis) the MLL/FOXO3A was present in up to 90% of BM cells including myeloid lineage, suggesting that the fusion arose in a multipotent progenitor. To identify potential "second hit" precipitating sALL we compared DNA in preleukemic versus fully leukemic samples. The analysis revealed a 10 Mb gain on 19q13.32 in the sALL, absent in the preleukemic specimen. These data provide insight into the dynamics of leukemogenesis in secondary leukemia with MLL rearrangement.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pré-Leucemia
/
Leucemia-Linfoma Linfoblástico de Células Precursoras B
/
Leucemia Promielocítica Aguda
/
Proteína de Leucina Linfoide-Mieloide
/
Fusão Gênica
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Female
/
Humans
Idioma:
En
Revista:
Genes Chromosomes Cancer
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
República Tcheca