Myriam Alcalay
Myriam Alcalay
affiliation: IEO - Istituto Europeo di Oncologia
research area(s): Cancer Biology, Genetics And Genomics
Course: Molecular Medicine: Molecular Oncology and Computational Biology
University/Istitution: Università di Milano, UNIMI-SEMM
High-throughput technologies are the most powerful tools for attempting holistic approaches in the post-genome era, and are rapidly becoming essential for the discovery and analysis of genetic networks underlying cancer. The use of microarrays and to study specific gene expression patterns in cancer model systems is a well established procedure. More recent technological advancements, including next-generation sequencing, have allowed for a more comprehensive analysis of complex molecular interactions that accompany 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 oncogenomics.

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 leukemogenesis. Our approach includes the integration of data deriving from gene expression profiling, analysis of transcription factor binding sites through chromatin immunoprecipitation coupled to deep sequencing (ChIP-seq), identification of histone modifications and proteomic analysis of transcriptional complexes containing leukemia-associated oncoproteins. Furthermore, we are specifically analysing the oncogene-induced activation of stem-cell signalling pathways in leukemia.
1)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.
2)N. Meani and M. Alcalay:
Role of nucleophosmin in acute myeloid leukemia.
Expert Reviews in anticancer Therapy, 2009, Sep;9(9):1283-94.
3)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.
4)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.
5)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).
6) 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.
7) 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.
8) 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.
9)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.
10) 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.
11) 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.
12) 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.
No projects are available to students for the current accademic year.