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

TY - JOUR

T1 - Independent prognostic value of BCR-ABL1-like signature and IKZF1 deletion, but not high CRLF2 expression, in children with B-cell precursor ALL

AU - van der Veer, Arian

AU - Waanders, Esmé

AU - Pieters, Rob

AU - Willemse, Marieke E

AU - Van Reijmersdal, Simon V

AU - Russell, Lisa J

AU - Harrison, Christine J

AU - Evans, William E

AU - van der Velden, Vincent H J

AU - Hoogerbrugge, Peter M

AU - Van Leeuwen, Frank

AU - Escherich, Gabriele

AU - Horstmann, Martin A

AU - Mohammadi Khankahdani, Leila

AU - Rizopoulos, Dimitris

AU - De Groot-Kruseman, Hester A

AU - Sonneveld, Edwin

AU - Kuiper, Roland P

AU - Den Boer, Monique L

PY - 2013/10/10

Y1 - 2013/10/10

N2 - 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.

AB - 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.

KW - Adolescent

KW - Child

KW - Child, Preschool

KW - Female

KW - Fusion Proteins, bcr-abl

KW - Humans

KW - Ikaros Transcription Factor

KW - Incidence

KW - Infant

KW - Male

KW - Precursor B-Cell Lymphoblastic Leukemia-Lymphoma

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma

KW - Predictive Value of Tests

KW - Prognosis

KW - Receptors, Cytokine

KW - Recurrence

KW - Risk Factors

U2 - 10.1182/blood-2012-10-462358

DO - 10.1182/blood-2012-10-462358

M3 - SCORING: Journal article

C2 - 23974192

VL - 122

SP - 2622

EP - 2629

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 15

ER -