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

Arian van der Veer, Esmé Waanders, Rob Pieters, Marieke E Willemse, Simon V Van Reijmersdal, Lisa J Russell, Christine J Harrison, William E Evans, Vincent H J van der Velden, Peter M Hoogerbrugge, Frank Van Leeuwen, Gabriele Escherich, Martin A Horstmann, Leila Mohammadi Khankahdani, Dimitris Rizopoulos, Hester A De Groot-Kruseman, Edwin Sonneveld, Roland P Kuiper, Monique L Den Boer

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)2622-9
Aantal pagina's8
TijdschriftBlood
Volume122
Nummer van het tijdschrift15
DOI's
StatusGepubliceerd - 10 okt. 2013
Extern gepubliceerdJa

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