Abstract 1491: Expression of osteopontin splicing isoforms in childhood B-cell precursor acute lymphoblastic leukemia

Abstract

Abstract Osteopontin (OPN) suffers alternative splicing generating three OPN splicing isoforms (OPN-SI), named OPNa, OPNb and OPNc. However, OPN-SI roles in hematological malignancies (HMs) are still under investigation. Detection of specific gene rearrangements allows the identification of relevant prognostic subgroups of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Patients harbouring the ETV6-RUNX1 rearrangement are classified as a good prognostic subgroup, while those with the KMT2A-AFF1 fusion are included into poor prognostic subgroup. This work aimed to analyze the expression levels of OPN-SI in BCP-ALL cell lines and patient samples. We tested 4 BCP-ALL cell lines: 207, ALL-PO, RS4;11 and REH. Patient samples included 28 samples from patients harbouring the ETV6-RUNX1 fusion and 26 samples presenting the KMT2A-AFF1 rearrangement. We found that these three OPN-SIs are expressed in all BCP-ALL cell lines and in 70% of both patient prognostic subgroups tested. Both 207 and REH cell lines displayed higher OPNc and OPNb levels than OPNa. We found that OPNc is expressed in higher levels than OPNb and OPNa in unfavorable prognostic subgroup and is also overexpressed in relation to OPNc levels in relation to the ETV6-RUNX1 fusion the comparative subgroup. Interestingly, we found that higher OPNc transcriptional levels are associated with poor prognostic features, such as central nervous system (CNS), initial white blood cell counting and high risk of relapse. In conclusion, we found that the three tested OPN-SI are expressed in most tested BCP-ALL cell lines and BCP-ALL human samples. Since higher OPNc levels are associated to prognostic features, our data provide early evidence that these OPN-SIs could specifically contribute to step BCP-ALL progression. Further work should investigate their putative applications as additional risk-stratification and prognostic markers for BCP-ALL, as well as, their roles on modulating HM progression. Citation Format: Ana Clara Santos da Fonseca Bastos, Caroline Barbieri Blunck Blunck, Luciana Bueno Ferreira, Maria do Socorro Pombo-de-Oliveira, Mariana Emerenciano, Etel R. Gimba. Expression of osteopontin splicing isoforms in childhood B-cell precursor acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1491.