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Molecular characterization of acute lymphoblastic leukemia with high CRLF2 gene expression in childhood
Author(s) -
Schmäh Juliane,
Fedders Birthe,
PanzerGrümayer Renate,
Fischer Susanna,
Zimmermann Martin,
Dagdan Elif,
Bens Susanne,
Schewe Denis,
Moericke Anja,
Alten Julia,
Bleckmann Kirsten,
Siebert Reiner,
Schrappe Martin,
Stanulla Martin,
Cario Gunnar
Publication year - 2017
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.26539
Subject(s) - medicine , chromosomal translocation , gene , fusion gene , gene expression , cancer research , microbiology and biotechnology , biology , genetics
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.