The hemato-lymphopoietic system represents a model for hyerarchical organization of cell self-maintenance, development, replication and terminal differentiation. The concept of stem cell and clonal development has been discovered and applied first on human leukemias, back in 1967. I have been interested in normal hemato-lymphopoiesis and its malignant counterpart, and in particular, how developing B cells transit from uncommitted precursors to mature effector cells and which phenotypic transitions define discrete stages of differentiation. Understanding the differentiation program of normal hemato-lymphoid cells is crucial to understand how malignant growth is regulated.

Leukemogenesis and lymphomagenesis root in molecular disregulation of normal gene expression by genomic alterations, mostly chromosomal rearrangements. Whether this leads to aberrant phenotypes or inappropriate expression of genes otherwise transiently expressed normally in minute subpopulations, is undefined, but has been the subject of a hot debate since the 1980's. I have used and developed immunofluorescent, immunohistochemical and flow cytometric techniques to identify cell lineages in human and experimental (murine) models of human malignancies. I and others have contributed tools for diagnostic immunohistochemistry in Pathology, in particular in establishing techniques and standards for the evaluation of growth fraction in tumors. Since 1994, I have established a close collaboration with Riccardo Dalla-Favera, providing pathologic expertise for the analysis of mouse models of lymphomagenesis and for the analysis of human lymphomas. I am directing a Pathology Core for an NIH-funded PO1 multiinstitutional project, devoted to the study of B cell maligancies. Within this collaboration, I contributed to the definition of the protooncogene bcl-6 as key gene for germinal center formation molecular pathogenesis of lymphoma and leukemia.

Selected Publications

D. Delia, G. Cattoretti, A. Bonati, S. Villa, F. DeBraud, M. Buscaglia. -Detection of the common acute lymphoblastic leukemia antigen (CALLA) on B cells from human fetal tissues. A multiple phenotypic characterization. -Clinical Experimental Immunology 59 : 305-314,1985. PubMed

G. Cattoretti, F. Rilke, S. Andreola, L. D'Amato, D. Delia. -p53 expression in breast cancer. -International Journal of Cancer vol 41: 178-183, 1988. PubMed

D. Delia, G. Cattoretti, N. Polli, E. Fontanella, A. Aiello, R. Giardini, F. Rilke, G. Della Porta. -CD1c but neither CD1a nor CD1b molecules are expressed on normal, activated and malignant human B cells: identification of a new B cell subset. - Blood, 72: 241-247, 1988. PubMed

G. Cattoretti, C. Parravicini, A. Bonati, M. Buscaglia, G. Zuliani, A. Plebani, D. Delia, F. Rilke. -Terminal deoxynucleotidyl transferase (TdT)-positive B-cell precursors in fetal lymph nodes and extrahemopoietic tissues. - European Journal of Immunology 19: 493-500, 1989. PubMed

G Cattoretti, M.H.G. Becker, G.Key, M. Duchrow, C. Schlüter and J. Gerdes -Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave processed formalin-fixed paraffin sections. - Journal of Pathology, 168: 357-363, 1992. PubMed

G. Cattoretti,  R. Schiró, A. Orazi,  D. Soligo, M. P. Colombo. -The bone marrow stroma in humans: anti nerve growth factor receptor antibodies selectively stain reticular cells in vivo and in vitro. -  Blood, 81: 1726-1738, 1993. PubMed

G. Cattoretti, S. Pileri, C. Parravicini, M.H.G. Becker, S. Poggi, C. Bifulco, G.Key,  L. D'Amato, E.Sabattini, E. Feudale, F. Reynolds, J. Gerdes, and F. Rilke. - Antigen unmasking on formalin-fixed, paraffin embedded tissue sections.-  J Pathol, 171: 83-98, 1993. PubMed

G. Cattoretti, CC Chang, K Cechova, J Zhang, BH Ye, B Falini, DC Louie, K Offitt, RSK Chaganti, R Dalla-Favera. - BCL-6 protein is expressed in germinal-center B cells. Blood 86: 45-53, 1995. PubMed

BH Ye, G Cattoretti, Q Shen, J Zhang, N Hawe, R DeWaard, C Leung, M Nouri-Shirazi, A Orazi, RSK Chaganti, P Rothman, AM Stall, PP Pandolfi, R Dalla-Favera. The BCL-6 proto-oncogene controls germinal center formation and Th2-type inflammation. Nature Genetics, 16(2):161-170, 1997. PubMed

Podsypanina K, Ellenson LH, Nemes A, Gu J, Tamura M, Yamada KM, Cordon-Cardo C, Cattoretti G, Fisher PE, Parsons R. Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. PNAS 96(4):1563-8, 1999. PubMed

Harris MB, Chang CC, Berton MT, Danial NN, Zhang J, Kuehner D, Ye BH, Kvatyuk M, Pandolfi PP, Cattoretti G, Dalla-Favera R, Rothman PB  Transcriptional Repression of Stat6-Dependent Interleukin-4-Induced Genes by BCL-6: Specific Regulation of Iepsilon Transcription and Immunoglobulin E Switching.  Mol Cell Biol 1999 Oct;19(10):7264-7275. PubMed

Toney LM, Cattoretti G, Graf JA, Maerghoub T, Pandolfi PP, Dalla-Favera R, Ye BH, Dent AL. BCL-6 regulates chemokine gene transcription in macrophages. Nature Immunology, 2000 1 (3), 214-220. PubMed

Angelin-Duclos C, Cattoretti G, Lin KI,  Calame K. Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo. J. Immunol. 2000 165: 5462-5471. PubMed

Hatzivassiliou G, Miller I, Takizawa J, Palanisamy N, Pulivarthi R, Iida S, Tagawa S, Russo J, Neri A, Cattoretti G, Clynes R, Mendelsohn C, Chaganti RSK,  Dalla-Favera R.IRTA1 and IRTA2, novel Immunoglobulin Superfamily Receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy. Immunity 14: 277-289, 2001. PubMed

Klein, U., Tu, Y., Stolovitzky, G.A., Mattioli, M., Cattoretti, G., Husson, H., Freedman, A., Inghirami, G., Cro, L., Baldini, L., Neri, A., Califano, A. and Dalla-Favera, R. (2001) Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells. J Exp Med 194:1625-38. PubMed

Gaboli, M., Kotsi, P.A., Gurrieri, C., Cattoretti, G., Ronchetti, S., Cordon-Cardo, C., Broxmeyer, H.E., Hromas, R. and Pandolfi, P.P. (2001) Mzf1 controls cell proliferation and tumorigenesis. Genes Dev 15:1625-30. PubMed

Book chapters:

Cattoretti G, Qing Fei. Application of the Antigen Retrieval Technique in experimental Pathology: from human to mouse. In Antigen Retrieval Techniques. Shi SR, Gy J and Taylor CR Editors. Eaton Publishing, Natick MA 2000. Pag. 165-179.