Abstract 3121: Osteopontin-c is overexpressed and mediates cell adhesion and proliferation in leukemia cell line with KMT2A-AFF1
| Autor: | Ana Clara Santos da Fonseca Bastos, Júlio César Santoro, Caroline Barbieri Blunck, Luciana Bueno Ferreira, Maria do Soccro Pombo-de-Oliveira, Mariana Emerenciano, Etel R. Gimba |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Cancer Research. 79:3121-3121 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Osteopontin (OPN) primary transcript suffers alternative splicing generating at least five OPN splicing isoforms (OPN-SI) named OPNa, OPNb, OPNc, OPN4 and OPN5. In solid tumors, total OPN (tOPN) expression has been correlated to several cancer features. However, OPN-SI roles in hematological malignancies are still under investigation. A hallmark of B-cell acute lymphoblastic leukemia (B-ALL) is the recurrence of specific gene rearrangements associated with prognostic risk stratification. Patients harbouring the KMT2A-AFF1 fusion gene are included into poor prognostic subgroup, with an overall survival rate of 50% and increased risk of extramedullary sites involvement. In B-ALL, it has been reported that tOPN support tumor dormancy and cell survival in response to chemotherapeutic drugs. However, the specific roles of OPN-SI have not been addressed. The aim of this study was to analyze the expression of OPN-SI in B-ALL samples and then investigate the role of the most overexpressed OPN-SI on modulating cellular and molecular aspects of B-ALL presenting KMT2A-AFF1. We found that OPNc is overexpressed in relation to OPNa and OPNb in patients with KMT2A-AFF1. In addition, OPNc transcript levels were associated with poor prognostic features, such as central nervous system infiltration, white blood cell counting and the high-risk group at diagnosis. In response to OPNc silencing in B-ALL cell lines, we found increased proliferation rates, as opposed to decreased cell adhesion properties over matrigel matrix. Our data evidenced that overexpressed OPNc in B-ALL with KMT2A-AFF1 is correlated to poor prognostic features and may modulate the leukemic phenotype by the decrease of cell proliferation while promoting cell adhesion. Further work should be conducted in order to evaluate OPNc putative application as an additional risk-stratification and prognostic marker for B-ALL and how OPNc could control leukemia development and progression. Note: This abstract was not presented at the meeting. Citation Format: Ana Clara Santos da Fonseca Bastos, Júlio César Santoro, Caroline Barbieri Blunck, Luciana Bueno Ferreira, Maria do Soccro Pombo-de-Oliveira, Mariana Emerenciano, Etel R. Gimba. Osteopontin-c is overexpressed and mediates cell adhesion and proliferation in leukemia cell line with KMT2A-AFF1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3121. |
| Databáze: | OpenAIRE |
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