Chemogenomic Profiling in Hematological Malignancies (HEM-Profiling 2021)

Primary outcomes

1. To evaluate the anti-cancer activity of bio-active compounds and derivatives present in FDA/EMA approved or investigator provided libraries, investigational molecules

   Time frame: At baseline

   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

2. To characterize molecular biomarkers for the identification of novel target therapies

   Time frame: At baseline

   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.

3. Correlate anti-cancer response with diagnostic (WHO classification) and molecular or novel omics features including cytogenetics, genomics, next generation or single cell technologies, radiomics.

   Time frame: At baseline

   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.