Experimental Hematology

redblood

Members:

Adalgisa Condoluci, MD
Alessio Bruscaggin, PhD
Davide Rossi, MD Group Leader
Francesca Guidetti, Technician
Gabriela Forestieri, Technician
Lodovico Terzi, Bioinformatics
Valeria Spina, PhD

Overview

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.

References

  • Rossi D1, Terzi-di-Bergamo L1, De Paoli L1, Cerri M1, Ghilardi G1, Chiarenza A2, Bulian P3, Visco C4, Mauro FR5, Morabito F6, Cortelezzi A7, Zaja F8, Forconi F9, Laurenti L10, Del Giudice I5, Gentile M6, Vincelli I11, Motta M12, Coscia M13, Rigolin GM14, Tedeschi A15, Neri A16, Marasca R17, Perbellini O18, Moreno C19, Del Poeta G20, Massaia M21, Zinzani PL22, Montillo M15, Cuneo A14, Gattei V3, Foà R5, Gaidano G1. Molecular prediction of durable remission after first-line fludarabine-cyclophosphamide-rituximab in chronic lymphocytic leukemia. Blood. 2015 Oct 15;126(16):1921-4. PMID: 26276669.

  • Famà R1, Bomben R2, Rasi S1, Dal Bo M2, Ciardullo C1, Monti S1, Rossi F2, D’Agaro T2, Zucchetto A2, Gattei V2, Gaidano G1, Rossi D1. Ibrutinib-naïve chronic lymphocytic leukemia lacks Bruton tyrosine kinase mutations associated with treatment resistance. Blood. 2014 Dec 11;124(25):3831-3. PMID: 25498455.
  • Piva R1, Deaglio S2, Famà R3, Buonincontri R2, Scarfò I1, Bruscaggin A3, Mereu E1, Serra S2, Spina V3, Brusa D2, Garaffo G1, Monti S3, Dal Bo M4, Marasca R5, Arcaini L6, Neri A7, Gattei V4, Paulli M8, Tiacci E9, Bertoni F10, Pileri SA11, Foà R12, Inghirami G13, Gaidano G3, Rossi D3. The Krüppel-like factor 2 transcription factor gene is recurrently mutated in splenic marginal zone lymphoma. Leukemia. 2015 Feb;29(2):503-7. PMID: 25283840.
  • Rossi D1, Khiabanian H, Spina V, Ciardullo C, Bruscaggin A, Famà R, Rasi S, Monti S, Deambrogi C, De Paoli L, Wang J, Gattei V, Guarini A, Foà R, Rabadan R, Gaidano G. Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia. Blood. 2014 Apr 3;123(14):2139-47. PMID: 24501221.

  • Rossi D1, Spina V, Bomben R, Rasi S, Dal-Bo M, Bruscaggin A, Rossi FM, Monti S, Degan M, Ciardullo C, Serra R, Zucchetto A, Nomdedeu J, Bulian P, Grossi A, Zaja F, Pozzato G, Laurenti L, Efremov DG, Di-Raimondo F, Marasca R, Forconi F, Del Poeta G, Gaidano G, Gattei V. Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia. Blood. 2013 Jun 13;121(24):4902-5. PMID: 23637131.