Unit research activity is aimed at understanding the molecular mechanisms responsible for the onset and progression of B cell lymphoproliferative disorders (leukemia and lymphomas), which represent most of the neoplasms of the immune system, accounting for 10% of all types of cancer. To this aim, the Unit intends to identify molecules and signal transduction pathways relevant to leukemic progression and that can potentially be used as diagnostic markers, prognostic factors or new potential therapeutic targets. To this end, research methodology is based on the integration of experimental results obtained, in vitro and in vivo, from the study of normal and neoplastic B lymphocytes.
This approach originates on the evidence that a better understanding of the physiological mechanisms of the immune system is essential to achieve a deeper understanding of the process of neoplastic transformation of B lymphocytes.
In recent years, the unit has been particularly interested in the pathogenesis of Chronic Lymphocytic Leukemia (CLL), the most frequent adult leukemia in the Western world. Group research activity is focused on the fundamental role played by the microenvironment in the pathogenesis of the disease by studying the surrounding non-neoplastic cells and the molecular interactions occurring with the leukemic clone that are responsible for the survival and expansion of the leukemia. Particular attention is given by our laboratory to the definition of the role played by the antigen receptor (B Cell Receptor) and its interaction with foreign or self antigens.
Furthermore, the unit has described the existence of a pre- leukemic condition named Monoclonal B lymphocytosis (MBL) which is being studied by this group, from a genetic and molecular point of view, as a model of tumor progression.
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McMahon KM, Scielzo C, Angeloni NL, Deiss-Yehiely E, Scarfo L, Ranghetti P, Ma S, Kaplan J, Barbaglio F, Gordon LI, Giles FJ, Shad Thaxton C, Ghia P. Synthetic high-density lipoproteins as targeted monotherapy for chronic lymphocytic leukemia. Oncotarget. 2017 Feb 14;8(7):11219-11227.
Stamatopoulos K, Agathangelidis A, Rosenquist R, Ghia P. Antigen receptor stereotypy in chronic lymphocytic leukemia. Leukemia. 2017 Feb;31(2):282-291.
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Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, Bairey O, Hillmen P, Bartlett NL, Li J, Simpson D, Grosicki S, Devereux S, McCarthy H, Coutre S, Quach H, Gaidano G, Maslyak Z, Stevens DA, Janssens A, Offner F, Mayer J, O'Dwyer M, Hellmann A, Schuh A, Siddiqi T, Polliack A, Tam CS, Suri D, Cheng M, Clow F, Styles L, James DF, Kipps TJ. RESONATE-2 Investigators. Ibrutinib as initial therapy for patients with Chronic lymphocytic leukemia. N Engl J Med. 2015 Dec 17;373(25):2425-37.
Gounari M, Ntoufa S, Apollonio B, Papakonstantinou N, Ponzoni M, Chu CC, Rossi D, Gaidano G, Chiorazzi N, Stamatopoulos K, Ghia P. Excessive antigen reactivity may underlie the clinical aggressiveness of chronic lymphocytic leukemia stereotyped subset 8. Blood. 2015 Jun 4;125(23):3580-7.
Simonetti G, Bertilaccio MT, Veliz Rodriguez T, Apollonio B, Dagklis A, Rocchi M, Innocenzi A, Casola S, Winkler TH, Nitschke L, Ponzoni M, Caligaris-Cappio F, Ghia P. SIGLEC-G deficiency increases susceptibility to develop B-cell lymphoproliferative disorders. Haematologica. 2014 Aug;99(8):1356-64.
Vardi A, Dagklis A, Scarfò L, Jelinek D, Newton D, Bennett F, Almeida J, Rodriguez-Caballero A, Allgood S, Lanasa M, Cortelezzi A, Orlandi E, Veronese S, Montillo M, Rawstron A, Shanafelt T, Orfao A, Stamatopoulos K, Ghia P. Immunogenetics shows that not all MBL are equal: the larger the clone the more similar to CLL. Blood. 2013;121:4521-4528.
Dagklis A, Ponzoni M, Govi S, Cangi MG, Pasini E, Charlotte F, Vino A, Doglioni C, Davì F, Lossos IS, Ntountas I, Papadaki T, Dolcetti R, Ferreri AJ, Stamatopoulos K, Ghia P. Immunoglobulin gene repertoire in ocular adnexal lymphomas: hints on the nature of the antigenic stimulation. Leukemia. 2012;26:814-821.
Fazi C, Scarfò L, Pecciarini L, Cottini F, Dagklis A, Janus A, Talarico A, Scielzo C, Sala C, Toniolo D, Caligaris-Cappio F, Ghia P. General population low-count CLL-like MBL persist over time without clinical progression, though carrying the same cytogenetic abnormalities of CLL. Blood. 2011;118:6618-6625.