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Home » ... » Dipartimento di Oncologia Sperimentale » Experimental Haematology Unit

Experimental Haematology

Director

Myriam Alcalay

  • +39 02.94375.203
  • +39 02.94375.990

Activities

High-throughput technologies have become essential for the discovery and analysis of genetic networks underlying cancer. Recent technological advancements, in particular next-generation sequencing, allow for a more comprehensive analysis of complex molecular interactions that accompany neoplastic transformation and tumor progression. The concerted use of these approaches to discover and characterize genetic and epigenetic events that are relevant to oncogenesis is one of the current challenges in the field of functional genomics applied to cancer research.

  • Research projects

    We are using an integrated genomic approach to study the molecular basis of acute leukemias. In particular:

    • we are performing detailed analyses of transcriptional networks underlying normal hematopoietic differentiation and their subversion in the pathogenesis of acute leukemias caused by chromosomal translocations involving the AML1 gene. Our approach includes the generation of cell lines expressing recurrent AML1-fusion proteins (AML1/ETO, TEL/AML1, AML1/MDS1, AML1/PRDM16), analysis of their DNA binding patterns and associated chromatin status, the study of their capacity to interfere with the binding profiles of other regulators of hematopoiesis such as CEBPα and PU.1, and of their effects on nuclear architecture and regulation of mRNA and miRNA expression.
    • we are studying the activation of stem-cell signalling pathways in acute myeloid leukemia (AML) bearing mutations of the nucleophosmin (NPM1) through the analysis of the hematopoietic compartment in developing zebrafish that express mutant NPM1.
    • - we are investigating the molecular basis of chemoresistance in AML through mutational analysis of matched tumor samples from patients at diagnosis and relapse. Our results will be integrated in a database of genomic data from AML that is being compiled in our laboratory.

  • Publications (last 10 years)

    2014

    • S. Licciulli and M. Alcalay (2014). Nuclear Protein Pirin Negates the Cellular Senescence Barrier Against Cancer Development. Tumor Dormancy, Quiescence, and Senescence, Volume 2: Aging, Cancer, and Noncancer Pathologies. Edited by M.A. Hayat. Springer Science+Business Media Dordrech. DOI 10.1007/978-94-007-7726-2_14.

    2013

    • A. M. Gruszka and M. Alcalay (2013). PML/RARα Fusion Gene and Response to Retinoic Acid and Arsenic Trioxide Treatment. Handbook of Therapeutic Biomarkers in Cancer. Edited by Sherry X. Yang and Janet Dancey. Pan Stanford Publishing, ISBN: 9789814364652.
    • V. Gambino, G. De Michele, O. Venezia, P. Migliaccio, V. Dall'Olio, L. Bernard, S.P. Minardi, M.A. Fazia, D. Bartoli, G. Servillo, M. Alcalay, L. Luzi, M. Giorgio, H. Scrable, P.G. Pelicci, E. Migliaccio: Oxidative stress activates a specific p53 transcriptional response that regulates cellular senescence and aging. Aging Cell. 2013 Jun;12(3):435-45. doi: 10.1111/acel.12060. Epub 2013 Mar 27.
    • L. Riva, C. Ronchini, M. Bodini, F. Lo-Coco, S. Lavorgna, T. Ottone, G. Martinelli, I. Iacobucci, C. Tarella, A. Cignetti, S. Volorio, L. Bernard, A. Russo, G.E. Melloni, L. Luzi, M. Alcalay, G.I. Dellino, P.G. Pelicci: Acute promyelocytic leukemias share cooperative mutations with other myeloid-leukemia subgroups. Blood Cancer J. 2013 Sep 13;3:e147.

    2012

    • A. M. Gruszka and M. Alcalay (2012). Clinical and Biological Relevance of Gene Expression Profiling in Acute Myeloid Leukemia, Myeloid Leukemia - Clinical Diagnosis and Treatment, Steffen Koschmieder and Utz Krug (Ed.), ISBN: 978-953-307-886-1, InTech, Available from: http://www.intechopen.com/articles/show/title/clinical-and-biological-relevance-of-gene-expression-profiling-in-acute-myeloid-leukemia.
    • C. Giampietro, A. Taddei, M. Corada, G.M. Sarra-Ferraris, M. Alcalay, U. Cavallaro, F. Orsenigo, M.G. Lampugnani, E. Dejana: Overlapping and divergent signalling pathways of N- and VE-cadherin in endothelial cells. Blood, 2012, Mar 1;119(9):2159-70.
    • E. Pelosi, G. Castelli, I. Martin-Padura, V. Bordoni, S. Santoro, A. Conigliaro, A.M. Cerio, M De Santis Puzzonia, P. Marighetti, M. Biffoni, T. Alonzi, L. Amicone, M. Alcalay, F. Bertolini, U. Testa, M. Tripodi.: Human haemato-endothelial precursors: cord blood CD34+ cells produce haemogenic endothelium. PLoS One, 2012;7(12):e51109. doi: 10.1371/journal.pone.0051109. Epub 2012 Dec 4.

    2011

    • E. Colombo, M. Alcalay and P.G. Pelicci: Nucleophosmin and its complex network: a possible therapeutic target in hematological diseases. Oncogene, 2011, 2011 Jun 9;30(23):2595-609.
    • S. Licciulli, C. Luise, G. Scafetta, M. Capra, G. Giardina, P. Nuciforo, S. Bosari, G. Viale, C. Tonelli, L. Lanfrancone and M. Alcalay: Pirin inhibits cellular senescence in melanocytic cells. American Journal of Pathology, 2011, 178(5):2397-406.

    2010

    • S. Licciulli, V. Cambiaghi, G. Scafetta, A. M. Gruszka and M. Alcalay: Pirin downregulation is a feature of AML and leads to impairment of terminal myeloid differentiation. Leukemia, 2010 Feb;24(2):429-37.
    • S. Licciulli, C. Luise, A. Zanardi, L. Giorgetti, G. Viale, L. Lanfrancone, R. Carbone and M. Alcalay: Pirin delocalization in melanoma progression identified by high content immuno-detection based approaches. BMC Cell biology, 2010, 11:5.
    • M. Fanelli, S. Amatori, I. Barozzi, M. Soncini, R. Dal Zuffo, G. Bucci, M. Capra, M. Quarto, G. I. Dellino, C. Mercurio, M. Alcalay, G. Viale, P. G. Pelicci, S. Minucci: PAT-ChIP-Seq: a tool for the epigenetic profiling of formaldehyde fixed and paraffin embedded (FFPE) pathology samples. Proc Natl Acad Sci Usa, 2010, 14;107(50):21535-40.

    2009

    • A. Viale, F. De Franco, A. Orleth, V. Cambiaghi, V. Giuliani, D. Bossi, C. Ronchini, S. Ronzoni, I. Muradore, S. Monestiroli, A. Gobbi, M. Alcalay, S. Minucci and P. G. Pelicci: Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells. Nature. 2009 January 1, 457, 51-56.
    • N. Meani, F. Pezzimenti, G. Deflorian, M. Mione and M. Alcalay: The tumor suppressor PRDM5 regulates Wnt signaling at early stages of zebrafish development. PLoS ONE, 2009, 4(1):e4273.
    • N. Meani and M. Alcalay: Role of nucleophosmin in acute myeloid leukemia. Expert Reviews in anticancer Therapy, 2009, Sep;9(9):1283-94

    2008

    • A. Gardini, M. Cesaroni, L. Luzi, S. P. Minardi, E. Venturini, P. G. Pelicci and M. Alcalay: AML1/ETO oncoprotein is directed to AML1 binding regions and draws E-protein HEB onto its targets. PLoS Genetics, 2008, Nov;4 (11).

    2007

    • S. Senese, K. Zaragoza, S. Minardi, I. Muradore, S. Ronzoni, A. Passafaro, L. Bernard, G.F. Draetta, M. Alcalay, C. Seiser, S. Chiocca: A role for histone deacetylase 1 in human tumor cell proliferation. Mol Cell Biol. 2007 Jul;27(13):4784-95.
    • I. Fumasoni, N. Meani, D. Rambaldi, G. Scafetta, M. Alcalay, and F. D. Ciccarelli: Family expansion and gene rearrangements contributed to the functional specialization of PRDM genes in vertebrates. BMC Evol. Biol., 2007; Oct 4; 7: 187-198.

    2006

    • A.R. Mariano, E. Colombo, L. Luzi, P. Martinelli, S. Volorio, L. Bernard, N. Meani, R. Bergomas, M. Alcalay and P.G. Pelicci: Cytoplasmic localization of NPM in myeloid leukemias is dictated by gain-of-function mutations that create a functional nuclear export signal. Oncogene, 2006 Jul 20;25(31):4376-80.
    • E. Colombo, P. Martinelli, R. Zamponi, D. C. Shing, P. Bonetti, L. Luzi,, S. Volorio, L. Bernard, G. Pruneri, M. Alcalay, and P. G. Pelicci: Delocalization and Destabilization of the Arf Tumor Suppressor by the Leukemia-Associated NPM Mutant. Cancer Res. 2006 Mar, 66, 3044-3050.
    • M. Ceribelli, M. Alcalay, M. A. Viganò and R. Mantovani: Repression of New p53 Targets Revealed by ChIP on Chip Experiments. Cell Cycle, 2006 May;5(10):1102-10.
    • M. S. Carro, F. M. Spiga, M. Quarto, V. Di Ninni, S.Volorio, M. Alcalay and H. Müller: DEK expression is controlled by E2F and deregulated in diverse tumor types. Cell Cycle, 2006, Jun;5(11):1202-7.
    • B. Falini, M. P. Martelli, N. Bolli, R. Bonasso, E. Ghia, M. T. Pallotta, D. Diverio, I. Nicoletti, R. Pacini, A. Tabarrini, B. Verducci Galletti, R. Mannucci, G. Roti, R. Rosati, G. Specchia, A. Liso, E. Tiacci, M. Alcalay, L. Luzi, S. Volorio, L. Bernard, A. Guarini, S. Amadori, F. Mandelli, F. Pane, F. Lo Coco, G. Saglio, P. G. Pelicci, M. F. Martelli, and C. Mecucci: Immunohistochemistry predicts nucleophosmin (NPM) mutations in acute myeloid leukemia. Blood, 2006 Sep 15;108(6):1999-2005.

    2005

    • A. Martoriati, G. Doumont, M. Alcalay, E. Bellefroid, P. G. Pelicci & J.C. Marine: DAPK1, an activator of a p19ARF-p53 mediated apoptotic checkpoint, is a transcription target of p53. Oncogene, 2005 Feb 17;24(8):1461-6.
    • B. Falini, C. Mecucci, E. Tiacci, M. Alcalay, R. Rosati, L. Pasqualucci, R. La Starza, D. Diverio, E. Colombo, A. Santucci, B. Bigerna, R. Pacini, A. Pucciarini, A. Liso, M. Vignetti, P. Fazi, N. Meani, V. Pettirossi, G. Saglio, F. Mandelli, F. Lo-Coco, P.G. Pelicci, and M. F. Martelli, for the GIMEMA Study Group: Cytoplasmic Nucleophosmin in Acute Myelogenous Leukemia with a Normal Karyotype. New Engl J Med 2005;352:254-266.
    • F. Fazi, L. Travaglini, D. Carotti, F. Palitti, D. Diverio, M. Alcalay, S. McNamara, W.H. Miller Jr, F. Lo Coco, P.G. Pelicci and C. Nervi: Retinoic acid targets DNA-methyltransferases and histone deacetylases during APL blast differentiation in vitro and in vivo. Oncogene, 2005 Mar 10;24(11):1820-30.
    • M. Alcalay, E. Tiacci, R. Bergomas, B. Bigerna, E. Venturini, S. P. Minardi, N. Meani, D. Diverio, L. Bernard, L. Tizzoni, S. Volorio, L. Luzi, E. Colombo, F. Lo Coco, C. Mecucci, B. Falini and P. G. Pelicci: Acute Myeloid Leukemia bearing cytoplasmic nucleophosmin (NPMc+ AML) shows a distinct gene expression profile characterized by up-regulation of genes involved in stem cell maintenance. Blood. 2005 Aug 1;106(3):899-902.
    • N. Meani, S. P. Minardi, Silvia Licciulli, V. Gelmetti, F. Lo Coco, C. Nervi, P. G. Pelicci, H. Müller, and M. Alcalay: Molecular Signature of Retinoic Acid Treatment in Acute Promyleocytic Leukemia. Oncogene, 2005 May 5;24(20):3358-68.
    • Doumont G, Martoriati A, Beekman C, Bogaerts S, Mee PJ, Bureau F, Colombo E, Alcalay M, Bellefroid E, Marchesi F, Scanziani E, Pelicci PG, Marine JC.: G1 checkpoint failure and increased tumor susceptibility in mice lacking the novel p53 target Ptprv. EMBO J. 2005 Sep 7;24(17):3093-103.

    2004

    • G. Finocchiaro, P. Parise, S.P. Minardi, M. Alcalay, and H. Müller: GenePicker: Replicate analysis of Affymetrix gene expression microarrays. Bioinformatics, 2004 Dec 12;20(18):3670-2.
    • M. Masseroli, A. Stella, N. Meani, M. Alcalay, and F. Pinciroli: MyWEST: a new personal Web Extraction Software Tool for effective mining of web-interfaced biomolecular databanks. Bioinformatics, 2004 Dec 12;20(18):3326-35.

  • Funding

    • Associazione Italiana per la Ricerca sul Cancro (AIRC)
    • Ministero della Salute – Ricerca Finalizzata
    • Fondazione Umberto Veronesi (FUV)

UN PICCOLO GESTO E' PER NOI UN GRANDE AIUTO

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Università degli Studi di Milano Ecancer Medical Science IFOM-IEO Campus

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