Quick Search:

is currently disabled due to reindexing of the ZORA database. Please use Advanced Search.
uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Schmitz, M; Breithaupt, P; Scheidegger, N; Cario, G; Bonapace, L; Meissner, B; Mirkowska, P; Tchinda, J; Niggli, F K; Stanulla, M; Schrappe, M; Schrauder, A; Bornhauser, B C; Bourquin, J P (2011). Xenografts of highly resistant leukemia recapitulate the clonal composition of the leukemogenic compartment. Blood, 118(7):1854-1864.

Full text not available from this repository.

Abstract

Clonal evolution of the leukemogenic compartment may contribute to alter the therapeutic response in acute lymphoblastic leukemia (ALL). Using xenotransplantation of primary leukemia cells, we evaluated the phenotypic and genetic composition of de novo resistant very high risk precursor B-cell ALL, a subgroup defined by the persistence of minimal residual disease despite intensive chemotherapy. Analysis of copy number alterations (CNAs) showed that the xenografted leukemia, even when reconstituted from 100 cells, remained highly related to the diagnostic sample, with minor changes in CNAs, mostly deletions, emerging in most cases in the first passage into mice. At the single-cell level, the pattern of monoallelic and biallelic deletions of the CDKN2A locus revealed distinct leukemia subpopulations, which were reproducibly tracked in xenografts. In most very high risk ALL cases, the predominant diagnostic clones were reconstituted in xenografts, as shown by multiplex polymerase chain reaction analysis of immunoglobulin and T-cell receptor loci. In other cases, the pattern in CNAs and immunoglobulin and T-cell receptor rearrangement was less concordant in xenografts, suggesting the outgrowth of subclones. These results unequivocally demonstrate the existence of clonally closely related but distinct subsets of leukemia initiating cells in ALL, which has important implications for drug development and preclinical disease modeling.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
DDC:610 Medicine & health
Language:English
Date:2011
Deposited On:15 Jan 2012 22:01
Last Modified:27 Nov 2013 18:13
Publisher:American Society of Hematology
ISSN:0006-4971
Publisher DOI:10.1182/blood-2010-11-320309
PubMed ID:21670474
Citations:Web of Science®. Times Cited: 15
Google Scholar™
Scopus®. Citation Count: 18

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page