title: Presence of the P2RY8-CRLF2 rearrangement is associated with a poor prognosis in non-high-risk precursor B-cell acute lymphoblastic leukemia in children treated according to the ALL-BFM 2000 protocol.
abstract: High-level expression of the cytokine receptor-like factor 2 gene, CRLF2, in precursor B-cell acute lymphoblastic leukemia (pB-ALL) was shown to be caused by a translocation involving the IGH@ locus or a deletion juxtaposing CRLF2 with the P2RY8 promoter. To assess its possible prognostic value, CRLF2 expression was analyzed in 555 childhood pB-ALL patients treated according to the Acute Lymphoblastic Leukemia Berlin-Frankfurt-Münster 2000 (ALL-BFM 2000) protocol. Besides CRLF2 rearrangements, high-level CRLF2 expression was seen in cases with supernumerary copies of the CRLF2 locus. On the basis of the detection of CRLF2 rearrangements, a CRLF2 high-expression group (n = 49) was defined. This group had a 6-year relapse incidence of 31% plus or minus 8% compared with 11% plus or minus 1% in the CRLF2 low-expression group (P = .006). This difference was mainly attributable to an extremely high incidence of relapse (71% +/- 19%) in non-high-risk patients with P2RY8-CRLF2 rearrangement. The assessment of CRLF2 aberrations may therefore serve as new stratification tool in Berlin-Frankfurt-Münster-based protocols by identifying additional high-risk patients who may benefit from an intensified and/or targeted treatment.
authors.affiliation: Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, Kiel, Germany. g.cario@pediatrics.uni-kiel.de
authors.forename: Gunnar
authors.initials: G
authors.lastname: Cario
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Renja
authors.initials: R
authors.lastname: Romey
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Inga
authors.initials: I
authors.lastname: Vater
authors.forename: Jochen
authors.initials: J
authors.lastname: Harbott
authors.forename: André
authors.initials: A
authors.lastname: Schrauder
authors.forename: Anja
authors.initials: A
authors.lastname: Moericke
authors.forename: Shai
authors.initials: S
authors.lastname: Izraeli
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasaka
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
mesh_terms: D002648:Child; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D011379:Prognosis; D018121:Receptors, Cytokine / Q000235:genetics*; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C498762:CRLF2 protein, human; D018121:Receptors, Cytokine; D018048:Receptors, Purinergic P2