The tumor cell cytoskeleton activity and the cross-talk with the microenvironment have a central role in cancer. The interactions between leukemic cells and the microenvironment are extremely dynamic and depend on the continuous re-circulation and homing into the lymphoid tissues where leukemic cells origin and grow.

Chronic Lymphocytic Leukemia (CLL), the adult most frequent B-cell malignancy and still an incurable blood cancer, is a pragmatic example.

Understanding the mechanisms that account for the molecular and cellular interactions occurring among leukemic cells and the microenvironment is expected to lead to new therapeutic strategies.

In particular, in this general scenario, the expression, activation and function of hemopoietic-cell-lineage specific 1 (HS1) protein conceivably play a crucial role. Elucidating this role might offer new chances for targeted therapy in lymphoid malignancies.

Curriculum Vitae

Education
2009-2012 PhD in Physiology, Università degli Studi di Milano, Supervisors: Dr. Valeria Caiolfa, Prof. Antonio Malgaroli
2005-2007 Master in Biotechnology with Specialization in Diagnostic Biotecnology, Università Vita-Salute San Raffaele, Milano Tutors: Prof. Federico Caligaris-Cappio, Prof. Paolo Ghia. This title was obtained in parallel with the research activity
1997-2001 Bachelor in Biotechnology, Università degli Studi di Genova, Tutors: Prof. Lorenzo Moretta, Dr. Roberto Biassoni

Current Positions
2012- present Project Leader – Laboratory of Lymphoid Malignancies, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan

Previous Position
2009- 2012 PhD Student – Physiology, Università degli Studi di Milano
2011 Visiting Scientist – Microscopy Unit (Dr. Valeria Caiolfa), CNIC (Fundación Centrom Nacional de Investigaciones Cardiovasculares Carlos III), Madrid, Spain
2003- 2009 Fellow – Laboratory of Lymphoid Malignancies, Division of Molecular Oncology, San Raffaele Scientific Institute, Milan
2003 Visiting fellow- Department of Medical Oncology (Dott. Angelo Cardoso), Dana Farber Cancer Institute, Harvard Medical School, Boston USA
2001 -2002 Fellow – Cancer Immunology Laboratory, Institute for Cancer Research and Treatment (IRCC), Candiolo, Italy

Teaching Activities
2013-present Instructor and Coordinator of the course: “Experimental models of translational research on Leukemia and Lymphomas ” at Università Vita-Salute San Raffaele

Fellowships and AWARDS
2010 Two years Research Fellowship from European Hematology Association, the amount of 72,000 Euro for salary and supplies

2007 Award for scientific merits at the “4th International Leukocyte Signal Transduction Workshop: Clinical implications of signaling pathways”, Rhodes, Greece

2004 Three years fellowship from Fondazione italiana ricerca sul cancro (FIRC)

2016  Three year grant My first grant AIRC

Organization of Scientific Meetings

2009 Attendant and Tutor in the session of TIRF Microscopy practice. Cordinator: Dott. Valeria Caiolfa Principles of Fluorescence Techniques II, Madrid, Spagna

Patent
2006 Patent title: “ Hematopoietic lineage cell specific protein (HS1) as a marker for lymphoid malignancy”.
International publication number: WO 2006/129203 A2. Inventors: Caligaris-Cappio Federico, Scielzo Cristina, Ghia Paolo, Alessio Massimo

Conferences
From 2005 I have been invited as a speaker to important international conferences including EHA annual meetings, iWCLL (international workshop on Chronic Lymphocytic Leukemia) and ICI (International congress in Immunology) on the topics: Leukemia, B cell biology and Cytoskeleton activity.

Research Activity

Our Research Unit is involved in several projects aiming at dissecting the molecular mechanisms responsible for the development and progression of lymphoid malignancies originating from B-lymphocytes. In particular our main focuses are:

  1. The molecular and functional characterization of normal and leukemic B -lymphocytes in order to dissect the natural history of the disease
  2. Define new prognostic parameters and identify new molecular targets to develop novel therapeutic approaches

III.  Study the tumor microenvironment

In particular Dr Scielzo research aims at elucidating the function of hemopoietic-cell-lineage specific 1 (HS1), a central cytoskeleton regulator in Chronic Lymphocytic Leukemia (CLL) with a strong prognostic value. Previous data from our Unit show that that interfering with HS1 expression and activity significantly impacts on the progression and homing of CLL cells.

Publications

1. Targeting Macrophages Sensitizes Chronic Lymphocytic Leukemia to Apoptosis and Inhibits Disease
Progression.
Galletti G, Scielzo C, Barbaglio F, Rodriguez TV, Riba M, Lazarevic D, Cittaro D, Simonetti G, Ranghetti P,
Scarfò L, Ponzoni M, Rocchi M, Corti A, Anselmo A, van Rooijen N, Klein C, Ries CH, Ghia P, De Palma M,
Caligaris-Cappio F, Bertilaccio MT. Cell Rep. 2016 Feb 10. pii: S2211-1247(16)30020-1.

2. HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment.
Valsecchi R, Coltella N, Belloni D, Ponente M, Ten Hacken E, Scielzo C, Scarfò L, Bertilaccio MT, Brambilla
P, Lenti E, Martinelli Boneschi F, Brendolan A, Ferrero E, Ferrarini M, Ghia P, Tonon G, Ponzoni M,
Caligaris Cappio F, Bernardi R. Blood. 2016 Jan 29.

3. Establishment and Characterization of PCL12, a Novel CD5+ Chronic Lymphocytic Leukaemia Cell Line.
Agathangelidis A, Scarfò L, Barbaglio F, Apollonio B, Bertilaccio MT, Ranghetti P, Ponzoni M, Leone G, De
Pascali V, Pecciarini L, Ghia P, Caligaris-Cappio F, Scielzo C*. PLoS One. 2015 Jun 25;10(6):e0130195 *
corresponding author

4. Apollonio B, Bertilaccio MT, Restuccia U, Ranghetti P, Barbaglio F, Ghia P, Caligaris-Cappio F, Scielzo C.
From a 2DE-gel spot to protein function: lesson learned from HS1 in chronic lymphocytic leukemia. J Vis
Exp. 2014 Oct 19;(92):e51942

5. How the microenvironment wires the natural history of chronic lymphocytic leukemia. Caligaris-Cappio F,
Bertilaccio MT, Scielzo C. Semin Cancer Biol. 2014 Feb;24:43-8.

6. Targeting B-cell anergy in chronic lymphocytic leukemia. Apollonio B, Scielzo C, Bertilaccio MT, Ten
Hacken E, Scarfò L, Ranghetti P, Stevenson F, Packham G, Ghia P, Muzio M, Caligaris-Cappio F. Blood.
2013 May 9;121(19):3879-88, S1-8.

7. Targeting the LYN/HS1 signaling axis in chronic lymphocytic leukemia.ten Hacken E*, Scielzo C*,
Bertilaccio MT, Scarfò L, Apollonio B, Barbaglio F, Stamatopoulos K, Ponzoni M, Ghia P, Caligaris-Cappio
F. Blood. 2013 Mar 21;121(12):2264-73.*authors equally contributed

8. Xenograft models of chronic lymphocytic leukemia: problems, pitfalls and future directions.
Bertilaccio MT, Scielzo C, Simonetti G, Ten Hacken E, Apollonio B, Ghia P, Caligaris-Cappio F. Leukemia.
2013 Mar;27(3):534-40.

9. General population low-count CLL-like MBL persists over time without clinical progression, although
carrying the same cytogenetic abnormalities of CLL. 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. Blood. 2011 Dec
15;118(25):6618-25. doi: 10.1182/blood-2011-05-357251

10. The functional in vitro response to CD40 ligation reflects a different clinical outcome in patients with chronic
lymphocytic leukemia. Scielzo C, Apollonio B, Scarfò L, Janus A, Muzio M, Ten Hacken E, Ghia P,
Caligaris-Cappio F. Leukemia. 2011 Nov;25(11):1760-7.

11. CLL-like monoclonal B-cell lymphocytosis: are we all bound to have it? Scarfò L, Dagklis A, Scielzo C, Fazi
C, Ghia P.Semin Cancer Biol. 2010 Dec;20(6):384-90. doi: 10.1016/j. Sem cancer.2010.08.005. Review

12. How the microenvironment shapes chronic lymphocytic leukemia: the cytoskeleton connection.Scielzo C*,
Ten Hacken E, Bertilaccio MT, Muzio M, Calissano C, Ghia P, Caligaris-Cappio F. Leuk Lymphoma. 2010
Aug;51(8):1371-4. * corrisponding author

13. An overview of chronic lymphocytic leukaemia biology. Bertilaccio MT, Scielzo C, Muzio M, Caligaris-
Cappio F. Best Pract Res Clin Haematol. 2010 Mar;23(1):21-32. doi: 10.1016/j.beha.2009.12.005. Review.

14. HS1 has a central role in the trafficking and homing of leukemic B cells.Scielzo C, Bertilaccio MT, Simonetti
G, Dagklis A, ten Hacken E, Fazi C, Muzio M, Caiolfa V, Kitamura D, Restuccia U, Bachi A, Rocchi M,
Ponzoni M, Ghia P, Caligaris-Cappio F. Blood. 2010 Nov 4;116(18):3537-46.

15. MicroRNA and proliferation control in chronic lymphocytic leukemia: functional relationship between miR-
221/222 cluster and p27. Frenquelli M, Muzio M, Scielzo C, Fazi C, Scarfò L, Rossi C, Ferrari G, Ghia P,
Caligaris-Cappio F. Blood. 2010 May 13;115(19):3949-59.

16. A novel Rag2-/-gammac-/–xenograft model of human CLL.Bertilaccio MT, Scielzo C, Simonetti G, Ponzoni
M, Apollonio B, Fazi C, Scarfò L, Rocchi M, Muzio M, Caligaris-Cappio F, Ghia P. Blood. 2010 Feb
25;115(8):1605-9.

17. Expression and function of toll like receptors in chronic lymphocytic leukaemia cells.Muzio M, Scielzo C,
Bertilaccio MT, Frenquelli M, Ghia P, Caligaris-Cappio F. Br J Haematol. 2009 Feb;144(4):507-16.

18. The immunoglobulin gene repertoire of low-count chronic lymphocytic leukemia (CLL)-like monoclonal B
lymphocytosis is different from CLL: diagnostic implications for clinical monitoring. Dagklis A, Fazi C, Sala
C, Cantarelli V, Scielzo C, Massacane R, Toniolo D, Caligaris-Cappio F, Stamatopoulos K, Ghia P. Blood.
2009 Jul 2;114(1):26-32.

19. Constitutive activation of distinct BCR-signaling pathways in a subset of CLL patients: a molecular signature
of anergy. Muzio M, Apollonio B, Scielzo C, Frenquelli M, Vandoni I, Boussiotis V, Caligaris-Cappio F, Ghia
P. Blood. 2008 Jul 1;112(1):188-95.

20. From normal to clonal B cells: Chronic lymphocytic leukemia (CLL) at the crossroad between neoplasia and
autoimmunity. Ghia P, Scielzo C, Frenquelli M, Muzio M, Caligaris-Cappio F. Autoimmun Rev. 2007
Dec;7(2):127-31. Review

21. Age-dependent accumulation of monoclonal CD4+CD8+ double positive T lymphocytes in the peripheral
blood of the elderly. Ghia P, Prato G, Stella S, Scielzo C, Geuna M, Caligaris-Cappio F. Br J Haematol. 2007
Dec;139(5):780-90.

22. Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia:
implications for the role of antigen selection in leukemogenesis. Murray F, Darzentas N, Hadzidimitriou A,
Tobin G, Boudjogra M, Scielzo C, Laoutaris N, Karlsson K, Baran-Marzsak F, Tsaftaris A, Moreno C,
Anagnostopoulos A, Caligaris-Cappio F, Vaur D, Ouzounis C, Belessi C, Ghia P, Davi F, Rosenquist R,
Stamatopoulos K. Blood. 2008 Feb 1;111(3):1524-33.

23. HS1 complexes with cytoskeleton adapters in normal and malignant chronic lymphocytic leukemia B cells.
Muzio M*, Scielzo C*, Frenquelli M, Bachi A, De Palma M, Alessio M, Ghia P, Caligaris-Cappio F.
Leukemia. 2007 Sep;21(9):2067-70. * authors equally contributed

24. Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer.
Venneri MA, De Palma M, Ponzoni M, Pucci F, Scielzo C, Zonari E, Mazzieri R, Doglioni C, Naldini
L.Blood. 2007 Jun 15;109(12):5276-85.

25. ZAP-70 is expressed by normal and malignant human B-cell subsets of different maturational stage. Scielzo C,
Camporeale A, Geuna M, Alessio M, Poggi A, Zocchi MR, Chilosi M, Caligaris-Cappio F, Ghia P. Leukemia.
2006 Apr;20(4):689-95.

26. Differential effects on CLL cell survival exerted by different microenvironmental elements.Ghia P, Circosta P,
Scielzo C, Vallario A, Camporeale A, Granziero L, Caligaris-Cappio F. Curr Top Microbiol Immunol.
2005;294:135-45. Review.

27. HS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor
prognoses.Scielzo C, Ghia P, Conti A, Bachi A, Guida G, Geuna M, Alessio M, Caligaris-Cappio F. J Clin
Invest. 2005 Jun;115(6):1644-5

28. CD38 modifications in chronic lymphocytic leukemia: are they relevant?Ghia P, Guida G, Scielzo C, Geuna
M, Caligaris-Cappio F. Leukemia. 2004 Oct;18(10):1733-5. Review.

29. Monoclonal CD5+ and CD5- B-lymphocyte expansions are frequent in the peripheral blood of the elderly.Ghia
P, Prato G, Scielzo C, Stella S, Geuna M, Guida G, Caligaris-Cappio F. Blood. 2004 Mar 15;103(6):2337-42.

30. The characterization of chemokine production and chemokine receptor expression reveals possible functional
cross-talks in AML blasts with monocytic differentiation.Cignetti A, Vallario A, Roato I, Circosta P, Strola G,
Scielzo C, Allione B, Garetto L, Caligaris-Cappio F, Ghia P. Exp Hematol. 2003 Jun;31(6):495-503.

31. The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at
risk of disease progression.Ghia P, Guida G, Stella S, Gottardi D, Geuna M, Strola G, Scielzo C, Caligaris-
Cappio F. Blood. 2003 Feb 15;101(4):1262-9

32. CD100/Plexin-B1 interactions sustain proliferation and survival of normal and leukemic CD5+ B
lymphocytes.Granziero L, Circosta P, Scielzo C, Frisaldi E, Stella S, Geuna M, Giordano S, Ghia P, Caligaris-
Cappio F. Blood. 2003 Mar 1;101(5):1962-9.

Book Publications
Chronic Lymphocytic Leukemia (Current Topics in Microbiology and Immunology, No. 294) PAG135
Milan, 5 April 2016