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Small sizes and indolent evolutionary dynamics challenge the potential role of P2RY8-CRLF2-harboring clones as main relapse-driving force in childhood ALL

Lookup NU author(s): Dr Lisa Russell

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Abstract

The P2RY8-CRLF2 fusion defines a particular relapse-prone subset of childhood acute lymphoblastic leukemia (ALL) in Italian Association of Pediatric Hematology and Oncology Berlin-Frankfurt-Munster (AIEOP-BFM) 2000 protocols. To investigate whether and to what extent different clone sizes influence disease and relapse development, we quantified the genomic P2RY8-CRLF2 fusion product and correlated it with the corresponding CRLF2 expression levels in patients enrolled in the BFM-ALL 2000 protocol in Austria. Of 268 cases without recurrent chromosomal translocations and high hyperdiploidy, representing approximately 50% of all cases, 67 (25%) were P2RY8-CRLF2 positive. The respective clone sizes were >= 20% in 27% and < 20% in 73% of them. The cumulative incidence of relapse of the entire fusion-positive group was clone size independent and significantly higher than that of the fusion-negative group (35% +/- 8% vs 13% +/- 3%, P = .008) and primarily confined to the non-high-risk group. Of 22 P2RY8-CRLF2-positive diagnosis/relapse pairs, only 4/8 had the fusion-positive dominant clone conserved at relapse, whereas none of the original 14 fusion-positive small clones reappeared as the dominant relapse clone. We conclude that the majority of P2RY8-CRLF2-positive clones are small at diagnosis and virtually never generate a dominant relapse clone. Our findings therefore suggest that P2RY8-CRLF2-positive clones do not have the necessary proliferative or selective advantage to evolve into a disease-relevant relapse clone. (Blood. 2012; 120(26): 5134-5142)


Publication metadata

Author(s): Morak M, Attarbaschi A, Fischer S, Nassimbeni C, Grausenburger R, Bastelberger S, Krentz S, Cario G, Kasper D, Schmitt K, Russell LJ, Potschger U, Stanulla M, Eckert C, Mann G, Haas OA, Panzer-Grumayer R

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2012

Volume: 120

Issue: 26

Pages: 5134-5142

Print publication date: 20/12/2012

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology

URL: http://dx.doi.org/10.1182/blood-2012-07-443218

DOI: 10.1182/blood-2012-07-443218


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Funding

Funder referenceFunder name
Help and Hope Foundation
KIK Textilien und Non-Food GmbH Austria
14129ONB Jubilaumsfonds
2010-03

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