Araceli Diez-Fraile1, Inge D’hont1, Pieter Van Vlierberghe2,3, Barbara De Moerloose1,3, Tim Lammens1,3

1Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
2Center for Medical Genetics Ghent, Ghent University, Ghent, Belgium
3Cancer Research Institute Ghent, Ghent, Belgium.


Objectives: The genetic translocation ETV6-RUNX1 (E/R) characterizes the second most common oncogenic subtype (25%) in children with pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Although this oncogenic subtype has cure rates of > 90% with contemporary treatment protocols, some patients will suffer from relapsed disease. Further understanding of the molecular biology of this group is necessary for the development of effective targeted therapies that will increase cure rates and reduce long-term side effects.
Methods: The PCLO transcript levels in samples from BCP-ALL cell lines and from pediatric patients were processed and analysed by total RNA sequencing and/or RT-qPCR. Furthermore, the mRNA expression levels of PCLO were evaluated “in silico" (Leukemia Gene Atlas “dataset Haferlach et al., 2010”).
Results: Total RNA sequencing from BCP-ALL cell lines (n=14) evidenced that the PCLO transcript was highly expressed within the E/R-positive REH cell line (n=1), while absent in other molecular groups. To further validate the initial findings, “in silico” gene expression analysis was performed using the mRNA expression profiles of PCLO in patients with BCP-ALL. In addition, mRNA expression levels of PCLO from E/R-positive and –negative BCP-ALL pediatric samples (n=64) and cell lines (n=12) were evaluated by RT-qPCR. Both results, “in silico” as well as RT-qPCR expression analysis, confirmed that the PCLO transcript is significantly overexpressed in the group of patients (“in silico” dataset as well as from the pediatric samples, n=25) and the cell lines (n=3) carrying the translocation.
Conclusion: The current findings show that PCLO is overexpressed in E/R-positive BCP-ALL. Further functional studies are needed to unveil the key mechanisms of PCLO in cells carrying the E/R translocation. Inhibitors of the aberrantly activated PCLO pathway may represent an interesting targeted therapy for patients with E/R-positive BCP-ALL.

PCLO IS OVEREXPRESSED IN ETV6-RUNX1-POSITIVE B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA