Clonal heterogeneity and chromosomal instability at disease presentation in high hyperdiploid acute lymphoblastic leukemia.

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Serval ID
serval:BIB_1D57061DCBAF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Clonal heterogeneity and chromosomal instability at disease presentation in high hyperdiploid acute lymphoblastic leukemia.
Journal
Cancer Genetics and Cytogenetics
Author(s)
Talamo Anna, Chalandon Yves, Marazzi Alfio, Jotterand Martine
ISSN
1873-4456 (Electronic)
ISSN-L
0165-4608
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
203
Number
2
Pages
209-214
Language
english
Abstract
Although aneuploidy has many possible causes, it often results from underlying chromosomal instability (CIN) leading to an unstable karyotype with cell-to-cell variation and multiple subclones. To test for the presence of CIN in high hyperdiploid acute lymphoblastic leukemia (HeH ALL) at diagnosis, we investigated 20 patients (10 HeH ALL and 10 non-HeH ALL), using automated four-color interphase fluorescence in situ hybridization (I-FISH) with centromeric probes for chromosomes 4, 6, 10, and 17. In HeH ALL, the proportion of abnormal cells ranged from 36.3% to 92.4%, and a variety of aneuploid populations were identified. Compared with conventional cytogenetics, I-FISH revealed numerous additional clones, some of them very small. To investigate the nature and origin of this clonal heterogeneity, we determined average numerical CIN values for all four chromosomes together and for each chromosome and patient group. The CIN values in HeH ALL were relatively high (range, 22.2-44.7%), compared with those in non-HeH ALL (3.2-6.4%), thus accounting for the presence of numerical CIN in HeH ALL at diagnosis. We conclude that numerical CIN may be at the origin of the high level of clonal heterogeneity revealed by I-FISH in HeH ALL at presentation, which would corroborate the potential role of CIN in tumor pathogenesis.
Keywords
Adolescent, Adult, Aged, Centromere/ultrastructure, Centrosome/ultrastructure, Child, Child, Preschool, Chromosome Mapping, Cloning, Molecular, Diploidy, Female, Humans, In Situ Hybridization, Fluorescence, Infant, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
Pubmed
Create date
21/12/2010 14:41
Last modification date
29/05/2020 6:08
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