Oncoematologia di precisione - Gruppo di Ricerca

Clinical and translational research activity is focused on (i) understanding of the molecular basis of hematologic malignancies; (ii) development, transfer and implementation of precision medicine approaches; (iii) molecular and clinical characterization of pre-malignant states.
Multi-omics and single-cell analysis are applied to characterize malignant clones, clonal hierarchies and pathways of clonal progression. The role of Microenvironment in promoting selective clonal expansion is investigated through single-cell RNA sequencing, and  3D scaffold culture models.
The evolutionary trajectories of malignant clones are analyzed via Patient-derived models (iPSCs) and CRISPR/Cas9-based genome editing to identify actionable vulnerabilities and to develop platforms for drug screening. Novel therapeutic targets are screened as a basis for Drug development  and innovative clinical trials, including cell- and antibody-mediated immunotherapy, and inhibition through small molecules.
Highly-sensitive, patient-specific minimal residual disease monitoring protocols are developed to guide early and pre-emptive therapeutic intervention with immunotherapy approaches.

• Gallì A., Todisco G., Catamo E., Sala C., Elena C., Pozzi S., Bono E., Ferretti V.V., Rizzo E., Molteni E., Zibellini S., Sarchi M., Boveri E., Ferrari J., Fiorelli N., Camaschella C., Gasparini P., Toniolo D., Cazzola M., Malcovati L. Relationship between clone metrics and clinical outcome in clonal cytopenia. Blood, 2021;
• Malcovati L., Stevenson K., Papaemmanuil E., Neuberg D., Bejar R., Boultwood J., Bowen D.T., Campbell P.J., Ebert B.L., Fenaux P., Haferlach T., Heuser M., Jansen J.H., Komrokji R.S., Maciejewski J.P., Walter M.J., Fontenay M., Garcia-Manero G., Graubert T.A., Karsan A., Meggendorfer M., Pellagatti A., Sallman D.A., Savona M.R., Sekeres M.A., Steensma D.P., Tauro S., Thol F., Vyas P., Van de Loosdrecht A.A., Haase D., Tüchler H., Greenberg P.L., Ogawa S., Hellstrom-Lindberg E., Cazzola M. SF3B1-mutant MDS as a distinct disease subtype: a proposal from the IWG for the Prognosis of MDS. Blood, 2020;
• Malcovati L., Gallì A., Travaglino E., Ambaglio I., Rizzo E., Molteni E., Elena C., Ferretti V.V., Catricalà S., Bono E., Todisco G., Bianchessi A., Rumi E., Zibellini S., Pietra D., Boveri E., Camaschella C., Toniolo D., Papaemmanuil E., Ogawa S., Cazzola M. Clinical significance of somatic mutation in unexplained blood cytopenia. Blood, 2017;
• • Klampfl T., Gisslinger H., Harutyunyan A.S., Nivarthi H., Rumi E., Milosevic J.D., Them N.C., Berg T., Gisslinger B., Pietra D., Chen D., Vladimer G.I., Bagienski K., Milanesi C., Casetti I.C., Sant'Antonio E., Ferretti V., Elena C., Schischlik F., Cleary C., Six M., Schalling M., Schönegger A., Bock C., Malcovati L., Pascutto C., Superti-Furga G., Cazzola M., Kralovics R. Somatic mutations of calreticulin in myeloproliferative neoplasms. The New England Journal of Medicine, 2013;
• Papaemmanuil E., Cazzola M., Boultwood J., Malcovati L., Vyas P., Bowen D., Pellagatti A., Wainscoat J.S., Hellstrom-Lindberg E., Gambacorti-Passerini C., Godfrey A.L., Rapado I., Cvejic A., Rance R., McGee C., Ellis P., Mudie L.J., Stephens P.J., McLaren S., Massie C.E., Tarpey P.S., Varela I., Nik-Zainal S., Davies H.R., Shlien A., Jones D., Raine K., Hinton J., Butler A.P., Teague J.W., Baxter E.J., Score J., Galli A., Della Porta M.G., Travaglino E., Groves M., Tauro S., Munshi N.C., Anderson K.C., El-Naggar A., Fischer A., Mustonen V., Warren A.J., Cross N.C., Green A.R., Futreal P.A., Stratton M.R., Campbell P.J., Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. The New England Journal of Medicine, 2011.

• AIRC - “Special Program Molecular Clinical Oncology 5 per mille”;
• Cancer Research UK – Accelerator Award; Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia - RICERCA CORRENTE.

• International Working Group for MDS & MDS/MPN;
• European MDS (EUMDS) Registry;
• European Reference Network – EuroBloodNet;
• European LeukemiaNet;
• Clinical Genome Program (ClinGen);
• GIMEMA – Gruppo Italiano Malattie Ematologiche dell’Adulto.