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Independent prognostic value of BCR-ABL1-like signature and IKZF1 deletion, but not high CRLF2 expression, in children with B-cell precursor ALL

Lookup NU author(s): Dr Lisa Russell, Professor Christine Harrison FRCPath FMedSci

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Abstract

Most relapses in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are not predicted using current prognostic features. Here, we determined the co-occurrence and independent prognostic relevance of 3 recently identified prognostic features: BCR-ABL1-like gene signature, deletions in IKZF1, and high CRLF2 messenger RNA expression (CRLF2-high). These features were determined in 4 trials representing 1128 children with ALL: DCOG ALL-8, ALL9, ALL10, and Cooperative ALL (COALL)-97/03. BCR-ABL1-like, IKZF1-deleted, and CRLF2-high cases constitute 33.7% of BCR-ABL1-negative, MLL wild-type BCP-ALL cases, of which BCR-ABL1-like and IKZF1 deletion (co)occurred most frequently. Higher cumulative incidence of relapse was found for BCR-ABL1-like and IKZF1-deleted, but not CRLF2-high, cases relative to remaining BCP-ALL cases, reflecting the observations in each of the cohorts analyzed separately. No relapses occurred among cases with CRLF2-high as single feature, whereas 62.9% of all relapses in BCR-ABL1-negative, MLL wild-type BCP-ALL occurred in cases with BCR-ABL1-like signature and/or IKZF1 deletion. Both the BCR-ABL1-like signature and IKZF1 deletions were prognostic features independent of conventional prognostic markers in a multivariate model, and both remained prognostic among cases with intermediate minimal residual disease. The BCR-ABL1-like signature and an IKZF1 deletion, but not CRLF2-high, are prognostic factors and are clinically of importance to identify high-risk patients who require more intensive and/or alternative therapies.


Publication metadata

Author(s): van der Veer A, Waanders E, Pieters R, Willemse ME, Van Reijmersdal SV, Russell LJ, Harrison CJ, Evans WE, van der Velden VHJ, Hoogerbrugge PM, Van Leeuwen F, Escherich G, Horstmann MA, Khankahdani LM, Rizopoulos D, De Groot-Kruseman HA, Sonneveld E, Kuiper RP, Den Boer ML

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2013

Volume: 122

Issue: 15

Pages: 2622-2629

Print publication date: 10/10/2013

Online publication date: 23/08/2013

Acceptance date: 10/06/2013

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology

URL: http://dx.doi.org/10.1182/blood-2012-10-462358

DOI: 10.1182/blood-2012-10-462358


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Funding

Funder referenceFunder name
KUN 2009-4298Dutch Cancer Society (KWF)
R37 CA36401National Institutes of Health National Cancer Institute
Kay Kendal Leukaemia Fund, United Kingdom
Pediatric Oncology Foundation Rotterdam
St. Jude Children's Research Hospital, Memphis, TN
2007-3718Dutch Cancer Society (KWF)
2010-138Sophia Foundation for Scientific Research (SSWO)

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