Precursor B cell acute lymphoblastic leukemia (BCP-ALL) is the most common childhood malignancy and represents the leading cause of cancer-related death in children and young adults. BCP-ALL arises from a monoclonal or oligoclonal expansion of malignant B cell precursors in the bone marrow and despite the overall progress in treatment, relapse occurs across the whole spectrum of all subtypes with an overall survival of 30%. We recently found that Che-1/AATF, an important RNA polymerase II binding protein involved in the regulation of gene transcription with anti-apoptotic activity in different tumour contests, exerts a pivotal role in BCP-ALL. Che-1 is highly expressed in a cohort of BCP-ALL patients at the onset of disease and at time of relapse, irrespective of genetic heterogeneity, but was barely detectable when patients obtained leukemia remission. Notably, Che-1 depletion strongly affected growth of BCP-ALL cells and sensitized to Adriamycin. With the aim to therapeutically inhibit Che-1 expression, overcoming the difficulty of the nuclear localization, and to find a technical approach available in in vivo models we focused on exosome-mediated delivery of RNA oligos. This experimental approach resulted in downregulation of Che-1 expression in BCP-ALL cell lines. The obtained result produced also an increase in PARP cleavage and a higher amount of cells in subG0-1 phase. Since part of this procedure is an already approved GMP-grade procedure, we will test the cooperation between exosome-mediated Che-1 downregulation and the current therapeutic treatments with the aim to develop a new applicable clinical approach, particularly in BCP-ALL relapsed patients.
29 maggio 2020, ore 12 online
Dr. Valentina Folgiero PhD, Dep. Onco-hematology, Bambino Gesù Children's Hospital Rome
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