The study will be conducted retrospectively and prospectively, using bone marrow (BM) or peripheral blood (PB) samples or biopsies of lymph nodes or tissues with metastatic involvement taken from previously stored samples here at the University Hospital of Parma or taken from patients that need to underwent diagnostic evaluation for a suspect or a defined diagnosis of hematological malignancies collected at the University Hospital of Parma.
Patient aged >1 year old, referred for evaluation to the University Hospital of Parma;
Retrospective study: previously patients with hematological malignancies;
Prospective study: 1) patients with clinical suspect of hematological malignancies which requires a diagnostic assessment using peripheral blood drawn, bone marrow aspirate/biopsy, lymph nodes biopsies or biopsies of tissues with metastatic involvement including liquor from rachicentesis, tissue aspirate etc. 2) patients with clinical suspect of relapsed/refractory onco-hematological disorder, which requires a diagnostic assessment using bone marrow aspirate/biopsy or biopsies of tissues with metastatic involvement including lymph nodes, liquor from rachicentesis, tissue aspirate etc. 3) patients that progress in blastic transformation from a chronic condition or suspect of relapsed/refractory hematological disease, which requires a diagnostic assessment using peripheral blood drawn, bone marrow aspirate/biopsy, lymph nodes biopsies or biopsies of tissues with metastatic involvement including liquor from rachicentesis, tissue aspirate etc;
Written informed consent. Retrospective study: informed consent will be signed during the first follow-up visit.
Age <1 year old
Patients who are unable to provide informed consent prior to any procedure for any reason.
Single group
Genetic, molecular and/or omics analyses
Other interventionThe focus of our scientific approach is based on genetic, molecular and/or omics analyses performed with new technologies (Nanostring, NGS, single cell technologies, radiomics)
To evaluate the anti-cancer activity of bio-active compounds and derivatives present in FDA/EMA approved or investigator provided libraries, investigational molecules
The study will be performed in malignant cells of a cohort of 250 patients with onco-hematological disorders obtained from a bone marrow aspirate/biopsy or biopsies of tissues with metastatic involvement including lymph nodes, liquor from rachicentesis, tissue aspirate etc. separated by a tissue-specific protocol: densitometry protocol for peripheral or bone marrow blood, tissue fractionation for tissue biopsies, precipitation for liquor. Cells will be than cultured in the presence or absence of small molecules derived from chemical library FDA/EMA approved, investigational molecules (monoclonal antibodies, antibody-drug conjugate, other experimental compounds). We will use miniaturized assays such cell culture in 384 multiwell plates to maximize the use of primary cells and to test simultaneously multiple concentrations of multiple drugs. We will perform several assays to assess cellular response to drug's perturbation such as: proliferation, cell cycle and apoptosis analysis
To characterize molecular biomarkers for the identification of novel target therapies
Thanks to genetic and molecular and/or omics analyses performed with new technologies (Nanostring, NGS, single cell technologies, radiomics), we propose to study novel molecular target that may be sensitive to the tested compounds in order to identify new target therapies.
Correlate anti-cancer response with diagnostic (WHO classification) and molecular or novel omics features including cytogenetics, genomics, next generation or single cell technologies, radiomics.
The completion of experiments described in aim 1 will give us the opportunity, for example, to extrapolate the IC50 (half maximal inhibitory concentration: a measure of the effectiveness of a substance in inhibiting a specific biological or biochemical function) dose for a small molecule of interest and correlate this value with clinical, cytogenetic, genomic and molecular features of that particular case. These data will be further compared with larger repository publicly available in the literature.
Click on the lead sponsor to view all of their trials.
Azienda Ospedaliero-Universitaria di Parma
Lead sponsor
University of Parma
Sponsor institution
