Open Access
Assessment of minimal residual disease by next generation sequencing in peripheral blood as a complementary tool for personalized transplant monitoring in myeloid neoplasms
(MDPI, 2020) Aguirre-Ruiz, Paula; Ariceta, Beñat; Viguria Alegría, María Cruz; Zudaire, María Teresa; Blasco-Iturri, Zuriñe; Arnedo, Patricia; Aguilera-Diaz, Almudena; Jauregui, Axier; Mañú, Amagoia; Prósper, Felipe; Mateos, María Carmen; Fernández-Mercado, Marta; Larráyoz, María José; Redondo, Margarita; Calasanz, María José; Bandrés Elizalde, Eva; Vázquez Urio, Iria; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Patients with myeloid neoplasms who relapsed after allogenic hematopoietic stem cell transplant (HSCT) have poor prognosis. Monitoring of chimerism and specific molecular markers as a surrogate measure of relapse is not always helpful; therefore, improved systems to detect early relapse are needed. We hypothesized that the use of next generation sequencing (NGS) could be a suitable approach for personalized follow-up post-HSCT. To validate our hypothesis, we analyzed by NGS, a retrospective set of peripheral blood (PB) DNA samples previously evaluated by high-sensitive quantitative PCR analysis using insertion/deletion polymorphisms (indel-qPCR) chimerism engraftment. Post-HCST allelic burdens assessed by NGS and chimerism status showed a similar time-course pattern. At time of clinical relapse in 8/12 patients, we detected positive NGS-based minimal residual disease (NGS-MRD). Importantly, in 6/8 patients, we were able to detect NGS-MRD at time points collected prior to clinical relapse. We also confirmed the disappearance of post-HCST allelic burden in non-relapsed patients, indicating true clinical specificity. This study highlights the clinical utility of NGS-based post-HCST monitoring in myeloid neoplasia as a complementary specific analysis to high-sensitive engraftment testing. Overall, NGS-MRD testing in PB is widely applicable for the evaluation of patients following HSCT and highly valuable to personalized early treatment intervention when mixed chimerism is detected.
Open Access
Epigenetic regulation of microRNAs in cancer: shortening the distance from bench to bedside
(MDPI, 2021) Pajares Villandiego, María Josefa; Alemany Cosme, Ester; Goñi Irigoyen, Saioa; Bandrés Elizalde, Eva; Palanca Ballester, Cora; Sandoval, Juan; Ciencias de la Salud; Osasun Zientziak
Cancer is a complex disease involving alterations of multiple processes, with both genetic and epigenetic features contributing as core factors to the disease. In recent years, it has become evident that non-coding RNAs (ncRNAs), an epigenetic factor, play a key role in the initiation and progression of cancer. MicroRNAs, the most studied non-coding RNAs subtype, are key controllers in a myriad of cellular processes, including proliferation, differentiation, and apoptosis. Furthermore, the expression of miRNAs is controlled, concomitantly, by other epigenetic factors, such as DNA methylation and histone modifications, resulting in aberrant patterns of expression upon the occurrence of cancer. In this sense, aberrant miRNA landscape evaluation has emerged as a promising strategy for cancer management. In this review, we have focused on the regulation (biogenesis, processing, and dysregulation) of miRNAs and their role as modulators of the epigenetic machinery. We have also highlighted their potential clinical value, such as validated diagnostic and prognostic biomarkers, and their relevant role as chromatin modifiers in cancer therapy.
Open Access
EVI1 controls proliferation in acute myeloid leukaemia through modulation of miR-1-2
(Nature Publishing Group, 2010-09-14) Gómez-Benito, María; Conchillo, Ana; García, M. A.; Vázquez Urio, Iria; Maicas, Miren; Vicente, Carmen; Cristobal, I.; Marcotegui, Nerea; García-Ortí, L.; Bandrés Elizalde, Eva; Calasanz, María José ; Alonso, M. M.; Odero, María D.; Ciencias; Zientziak; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Bakground: the EVI1(ecotropic virus integration site 1) gene codes for a zinc-finger transcription factor, whose transcriptional activation leads to a particularly aggressive form of acute myeloid leukaemia (AML). Although, EVI1 interactions with key proteins in hematopoiesis have been previously described, the precise role of this transcription factor in promoting leukaemic transformation is not completely understood. Recent works have identified specific microRNA (miRNA) signatures in different AML subgroups. However, there is no analysis of miRNAs profiles associated with EVI1 overexpression in humans. Methods: we performed QT-RT-PCR to assess the expression of 250 miRNAs in cell lines with or without EVI1 overexpression and in patient samples. We used ChIP assays to evaluated the possible binding of EVI1 binding to the putative miRNA promoter. Proliferation of the different cell lines transfected with the anti- or pre-miRs was quantified by MTT. Results: our data showed that EVI1 expression was significantly correlated with the expression of miR-1-2 and miR-133-a-1 in established cell lines and in patient samples. ChIP assays confirmed that EVI1 binds directly to the promoter of these two miRNAs. However, only miR-1-2 was involved in abnormal proliferation in EVI1 expressing cell lines. Conclusions: our data showed that EVI1 controls proliferation in AML through modulation of miR-1-2. This study contributes to further understand the transcriptional networks involving transcription factors and miRNAs in AML.
Open Access
Potency assessment of IFNγ-producing SARS-CoV-2- specific T cells from COVID-19 convalescent subjects
(Life Science Alliance, 2023) Gil Bescós, Rubén; Ostiz, Ainhoa; Zalba, Saioa; Tamayo Rodríguez, Ibai; Bandrés Elizalde, Eva; Rojas De Miguel, Elvira; Redondo, Margarita; Zabalza San Martín, Amaia; Ramírez, Natalia; Ciencias de la Salud; Osasun Zientziak
The development of new therapies for COVID-19 high-risk patients remains necessary to prevent additional deaths. Here, we studied the phenotypical and functional characteristics of IFN-γ producing-SARS-CoV-2-specific T cells (SC2-STs), obtained from 12 COVID-19 convalescent donors, to determine their potency as an off-the-shelf T cell therapy product. We found that these cells present mainly an effector memory phenotype, characterized by the basal expression of cytotoxicity and activation markers, including granzyme B, perforin, CD38, and PD-1. We demonstrated that SC2-STs could be expanded and isolated in vitro, and they exhibited peptide-specific cytolytic and proliferative responses after antigenic re-challenge. Collectively, these data demonstrate that SC2-STs can be a suitable candidate for the manufacture of a T cell therapy product aimed to treat severe COVID-19.

Bandrés Elizalde, Eva

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