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Pediatr Blood Cancer. 2017 Oct;64(10). doi: 10.1002/pbc.26539. Epub 2017 Apr 1.

Molecular characterization of acute lymphoblastic leukemia with high CRLF2 gene expression in childhood.

Author information

1
Department of Pediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany.
2
Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria.
3
Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
4
Institute of Human Genetics, Christian-Albrechts-University Kiel & University Medical Center Schleswig-Holstein, Kiel, Germany.
5
Institute of Human Genetics, University of Ulm, Ulm, Germany.

Abstract

BACKGROUND:

A high-level expression of the CRLF2 gene is frequent in precursor B-cell acute lymphoblastic leukemia (pB-ALL) and can be caused by different genetic aberrations. The presence of the most frequent alteration, the P2RY8/CRLF2 fusion, was shown to be associated with a high relapse incidence in children treated according to ALL-Berlin-Frankfurt-Münster (BFM) protocols, which is poorly understood. Moreover, the frequency of other alterations has not been systematically analyzed yet.

PROCEDURE:

CRLF2 mRNA expression and potential genetic aberrations causing a CRLF2 high expression were prospectively assessed in 1,105 patients treated according to the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP)-BFM ALL 2009 protocol. Additionally, we determined copy number alterations in selected B-cell differentiation genes for all CRLF2 high-expressing pB-ALL cases, as well as JAK2 and CRLF2 mutations.

RESULTS:

A CRLF2 high expression was detected in 26/178 (15%) T-cell acute lymphoblastic leukemia (T-ALL) cases, 21 of them (81%) had been stratified as high-risk patients by treatment response. In pB-ALL, a CRLF2 high expression was determined in 91/927 (10%) cases; the P2RY8/CRLF2 rearrangement in 44/91 (48%) of them, supernumerary copies of CRLF2 in 18/91 (20%), and, notably, the IGH/CRLF2 translocation was detected in 16/91 (18%). Remarkably, 7 of 16 (44%) patients with IGH/CRLF2 translocation had already relapsed. P2RY8/CRLF2- and IGH/CRLF2-positive samples (70 and 94%, respectively) were characterized by a high frequency of additional deletions in B-cell differentiation genes such as IKZF1 or PAX5.

CONCLUSION:

Our data suggest that this high frequency of genetic aberrations in the context of a high CRLF2 expression could contribute to the high risk of relapse in P2RY8/CRLF2- and IGH/CRLF2-positive ALL.

KEYWORDS:

CRLF2; IGH/CRLF2; P2RY8/CRLF2; acute lymphoblastic leukemia; prognosis

PMID:
28371317
DOI:
10.1002/pbc.26539
[Indexed for MEDLINE]

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