Two subgroups of CRLF2-overexpressing pediatric acute lymphoblastic leukemias differ in outcome and gene expression

J Schmäh; S Müller; F Grunz; H Harms; B Rotter; I Koch; G Kahl; P Winter; M Schrappe; M Stanulla; G Cario

doi:10.1055/s-0034-1374826

Two subgroups of CRLF2-overexpressing pediatric acute lymphoblastic leukemias differ in outcome and gene expression

J Schmäh ¹, S Müller ²^,³^,⁴, F Grunz ²^,³, H Harms ¹, B Rotter ², I Koch ⁴, G Kahl ²^,³, P Winter ², M Schrappe ¹, M Stanulla ⁵, G Cario ¹

¹Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel
²GenXPro GmbH, Frankfurt/Main
³Institute of Molecular BioScience, Goethe University, Frankfurt/Main
⁴Molecular Bioinformatics, Goethe University, Frankfurt/Main
⁵Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany

Abstract

^*These authors contributed similarly to the study.

Overexpression of the cytokine receptor-like factor 2 (CRLF2) gene in acute lymphoblastic leukemia (ALL) is caused by different aberrations like a deletion juxtaposing CRLF2 with the P2RY8 promoter, by a translocation involving the immunoglobulin heavy chain locus (IGH@), by supernumerary copies of the CRLF2 locus or by not yet identified causes. However, only the presence of the P2RY8-CRLF2 rearrangement is associated with a high incidence of relapse in CRLF2-overexpressing precursor B-cell ALL (pB-ALL) in children.

To investigate the different susceptibility to relapse, two groups of CRLF2-overexpressing patients, with and without P2RY8-CRLF2 fusion, were defined and analyzed by next-generation sequencing (NGS) based whole transcriptome profiling. Subsequently, promising candidate genes were validated in an independent patient cohort by real-time PCR (qPCR).

Notably, the group with P2RY8-CRLF2 rearrangement and high relapse rate revealed a distinct gene expression signature compared to the other CRLF2-overexpressing group. This may implicate a role of these differentially expressed genes in the development of relapse clones in the P2RY8-CRLF2 fusion group.