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IOR

An institute

affiliated to USI

Events

Experimental Hematology

Group Leader: Rossi Davide, MD, PhD

Modern advances in genomics and cancer biology, including our own studies, have produced an unprecedented body of knowledge regarding the molecular pathogenesis of mature B-cell tumors. Our group is working on the translation of newly discovered genetic lesions into the clinical practice as biomarkers for the refinement of the diagnostic workup, prognostic stratification and treatment of B-cell tumor patients.

Chronic lymphocytic leukaemia (CLL) treatment has dramatically improved with the approval of B-cell receptor (BCR) inhibitors and the clinical relevance of historical predictive/prognostic factors of CLL is questioned, at least in part, by these novel agents. The group is running translational studies aiming at discovering novel markers that can help the early prediction of sustained benefit vs loss of benefit from novel agents treatment in CLL.

Accessible and real-time genotyping for diagnostic, prognostic or treatment purposes is increasingly impelling in mature B-cell tumors lacking a leukemic phase. Cell-free DNA (cfDNA) is shed into the blood by tumor cells undergoing apoptosis and can be used as source of tumor DNA for the identification cancer-gene somatic mutations. By using highly sensitive ultra-deep NGS approaches to track the lymphoma genetic profile, we are comprehensively validating the “liquid biopsy” as a diagnostic tool to inform in real time mature B-cell tumor diagnosis, prognostication and treatment monitoring.

Members

Bocchetta Simone, PostDoc
Bruscaggin Alessio, PostDoc
Condoluci Adalgisa, Visiting Research Fellow
Forestieri Gabriela, Lab Technician
Marangon Marco, Lab Technician
Piffaretti Deborah, PostDoc
Pini Katia, Lab Technician
Pirosa Maria, Visiting Research Fellow
Rossi Davide, MD, PhD, Group Leader
Salehi Seyede Matin, PhD Student
Terzi Lodovico, MSc, Bioinformatician

Current Projects

  • Mechanisms of adaptation of chronic lymphocytic leukemia to ibrutinib
  • Understanding the mechanisms involved in NOTCH2/KLF2-mutated lymphoma
  • Treatment tailoring by optimized early residual disease assessment in classic Hodgkin lymphoma

Relevant Publications

  • Bonfiglio F, Bruscaggin A, Guidetti F, Terzi di Bergamo L, Faderl MR, Spina V, Condoluci A, Bonomini L, Forestieri G, Koch R, Piffaretti D, Pini K, Pirosa MC, Cittone MG, Arribas A, Lucioni M, Ghilardi G, Wu W, Arcaini L, Baptista MJ, Bastidas G, Bea S, Boldorini R, Broccoli A, Buhler MM, Canzonieri V, Cascione L, Ceriani L, Cogliatti SB, Corradini P, Derenzini E, Devizzi L, Dietrich S, Elia AR, Facchetti F, Gaidano G, Garcia JF, Gerber B, Ghia P, Gomes da Silva M, Gritti G, Guidetti A, Hitz F, Inghirami GG, Ladetto M, Lopez-Guillermo A, Lucchini E, Maiorana A, Marasca R, Matutes E, Meignin V, Merli M, Moccia AA, Mollejo M, Montalban C, Novak U, Oscier DG, Passamonti F, Piazza FA, Pizzolitto S, Rambaldi A, Sabattini E, Salles GA, Santambrogio E, Scarfo L, Stathis A, Stussi G, Geyer JT, Tapia G, Tarella C, Thieblemont C, Tousseyn T, Tucci A, Vanini G, Visco C, Vitolo U, Walewska R, Zaja F, Zenz T, Zinzani PL, Khiabanian H, Calcinotto A, Bertoni F, Bhagat G, Campo E, de Leval L, Dirnhofer S, Pileri SA, Piris MA, Traverse-Glehen A, Tzankov A, Paulli M, Ponzoni M, Mazzucchelli L, Cavalli F, Zucca E and Rossi D. Genetic and Phenotypic Attributes of Splenic Marginal Zone Lymphoma. Blood (2021). https://www.ncbi.nlm.nih.gov/pubmed/34653238.
  • Condoluci A, Terzi di Bergamo L, Langerbeins P, Hoechstetter MA, Herling CD, De Paoli L, Delgado J, Rabe KG, Gentile M, Doubek M, Mauro FR, Chiodin G, Mattsson M, Bahlo J, Cutrona G, Kotaskova J, Deambrogi C, Smedby KE, Spina V, Bruscaggin A, Wu W, Moia R, Bianchi E, Gerber B, Zucca E, Gillessen S, Ghielmini M, Cavalli F, Stussi G, Hess MA, Baumann TS, Neri A, Ferrarini M, Rosenquist R, Forconi F, Foa R, Pospisilova S, Morabito F, Stilgenbauer S, Dohner H, Parikh SA, Wierda WG, Montserrat E, Gaidano G, Hallek M and Rossi D. International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia. Blood (2020) 135, 1859-1869. https://www.ncbi.nlm.nih.gov/pubmed/32267500.
  • Spina V, Bruscaggin A, Cuccaro A, Martini M, Di Trani M, Forestieri G, Manzoni M, Condoluci A, Arribas A, Terzi-Di-Bergamo L, Locatelli SL, Cupelli E, Ceriani L, Moccia AA, Stathis A, Nassi L, Deambrogi C, Diop F, Guidetti F, Cocomazzi A, Annunziata S, Rufini V, Giordano A, Neri A, Boldorini R, Gerber B, Bertoni F, Ghielmini M, Stüssi G, Santoro A, Cavalli F, Zucca E, Larocca LM, Gaidano G, Hohaus S, Carlo-Stella C and Rossi D. Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma. Blood (2018) 131, 2413-2425. https://pubmed.ncbi.nlm.nih.gov/29449275/.
  • Spina V, Khiabanian H, Messina M, Monti S, Cascione L, Bruscaggin A, Spaccarotella E, Holmes AB, Arcaini L, Lucioni M, Tabbo F, Zairis S, Diop F, Cerri M, Chiaretti S, Marasca R, Ponzoni M, Deaglio S, Ramponi A, Tiacci E, Pasqualucci L, Paulli M, Falini B, Inghirami G, Bertoni F, Foa R, Rabadan R, Gaidano G and Rossi D. The genetics of nodal marginal zone lymphoma. Blood (2016) 128, 1362-1373. https://www.ncbi.nlm.nih.gov/pubmed/27335277.
  • Rossi D, Terzi-di-Bergamo L, De Paoli L, Cerri M, Ghilardi G, Chiarenza A, Bulian P, Visco C, Mauro FR, Morabito F, Cortelezzi A, Zaja F, Forconi F, Laurenti L, Del Giudice I, Gentile M, Vincelli I, Motta M, Coscia M, Rigolin GM, Tedeschi A, Neri A, Marasca R, Perbellini O, Moreno C, Del Poeta G, Massaia M, Zinzani PL, Montillo M, Cuneo A, Gattei V, Foa R and Gaidano G. Molecular prediction of durable remission after first-line fludarabine-cyclophosphamide-rituximab in chronic lymphocytic leukemia. Blood (2015) 126, 1921-1924. https://www.ncbi.nlm.nih.gov/pubmed/26276669.
  • Rossi D, Khiabanian H, Spina V, Ciardullo C, Bruscaggin A, Fama R, Rasi S, Monti S, Deambrogi C, De Paoli L, Wang J, Gattei V, Guarini A, Foa R, Rabadan R and Gaidano G. Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia. Blood (2014) 123, 2139-2147. https://www.ncbi.nlm.nih.gov/pubmed/24501221.
  • Rossi D, Trifonov V, Fangazio M, Bruscaggin A, Rasi S, Spina V, Monti S, Vaisitti T, Arruga F, Famà R, Ciardullo C, Greco M, Cresta S, Piranda D, Holmes A, Fabbri G, Messina M, Rinaldi A, Wang J, Agostinelli C, Piccaluga PP, Lucioni M, Tabbò F, Serra R, Franceschetti S, Deambrogi C, Daniele G, Gattei V, Marasca R, Facchetti F, Arcaini L, Inghirami G, Bertoni F, Pileri SA, Deaglio S, Foà R, Dalla-Favera R, Pasqualucci L, Rabadan R and Gaidano G. The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development. J Exp Med (2012) 209, 1537-1551. https://pubmed.ncbi.nlm.nih.gov/22891273/.
  • Rossi D, Fangazio M, Rasi S, Vaisitti T, Monti S, Cresta S, Chiaretti S, Del Giudice I, Fabbri G, Bruscaggin A, Spina V, Deambrogi C, Marinelli M, Famà R, Greco M, Daniele G, Forconi F, Gattei V, Bertoni F, Deaglio S, Pasqualucci L, Guarini A, Dalla-Favera R, Foà R and Gaidano G. Disruption of BIRC3 associates with fludarabine chemorefractoriness in TP53 wild-type chronic lymphocytic leukemia. Blood (2012) 119, 2854-2862. https://pubmed.ncbi.nlm.nih.gov/22308293/.
  • Rossi D, Rasi S, Fabbri G, Spina V, Fangazio M, Forconi F, Marasca R, Laurenti L, Bruscaggin A, Cerri M, Monti S, Cresta S, Fama R, De Paoli L, Bulian P, Gattei V, Guarini A, Deaglio S, Capello D, Rabadan R, Pasqualucci L, Dalla-Favera R, Foa R and Gaidano G. Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood (2012) 119, 521-529. https://www.ncbi.nlm.nih.gov/pubmed/22077063.
  • Rossi D, Bruscaggin A, Spina V, Rasi S, Khiabanian H, Messina M, Fangazio M, Vaisitti T, Monti S, Chiaretti S, Guarini A, Del Giudice I, Cerri M, Cresta S, Deambrogi C, Gargiulo E, Gattei V, Forconi F, Bertoni F, Deaglio S, Rabadan R, Pasqualucci L, Foà R, Dalla-Favera R and Gaidano G. Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. Blood (2011) 118, 6904-6908. https://pubmed.ncbi.nlm.nih.gov/22039264/.
  • Rossi D, Spina V, Deambrogi C, Rasi S, Laurenti L, Stamatopoulos K, Arcaini L, Lucioni M, Rocque GB, Xu-Monette ZY, Visco C, Chang J, Chigrinova E, Forconi F, Marasca R, Besson C, Papadaki T, Paulli M, Larocca LM, Pileri SA, Gattei V, Bertoni F, Foà R, Young KH and Gaidano G. The genetics of Richter syndrome reveals disease heterogeneity and predicts survival after transformation. Blood (2011) 117, 3391-3401. https://pubmed.ncbi.nlm.nih.gov/21266718/.

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