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Frezzato, Federica (2008) Coinvolgimento della proteina HS1 nella sopravvivenza dei linfociti B neoplastici di pazienti con leucemia linfatica cronica. [Tesi di dottorato]

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Abstract (inglese)

B-cell chronic lymphocytic leukemia (B-CLL) is the most common form of leukemia in adults and is characterized by the accumulation of clonal CD5+ B lymphocytes due to uncontrolled growth and resistance to apoptosis. Several protein kinase pathways have been claimed to be involved in the regulation of cell survival. We previously demonstrated that the Src kinase Lyn is overexpressed, constitutively active and anomalously distributed in malignant B cells as compared to normal B
lymphocytes. Our attention was subsequently focused on the 75 kDa HS1 protein, which is one of the major substrate of Lyn kinase upon BCR cross-linking and plays a crucial role in BCR-induced apoptosis in the mouse B lymphoma cell line WEHI-231. In the present study HS1 protein level was measured by western blotting analysis in 43 untreated B-CLL patients and in 26 normal controls. We found a significant difference in HS1 protein level between CLL and normal B cells, being mainly expressed in the leukemic patients with respect to normal controls (p<0.01). When we correlated HS1 protein level with prognostic factors, we observed that patients with more negative prognostic factors had a higher expression of HS1 protein regarding those with a better prognosis. We also analyzed HS1 in 10 CLL patients before and after in vivo therapy with fludarabine and cyclophosphamide; we found a significant reduction of both HS1 protein and mRNA levels in those patients which responded to therapy (n°=7) while non-responder patients (n°=3) did not show any change in HS1 levels.
Using confocal microscopy and subcellular cell fractionation, we observed an abnormal distribution of HS1 in leukemic cells with respect to normal B cells. In particular, the pattern of expression of HS1 appeared with a spotting distribution and a 4-7% aliquot of HS1 was present in the nucleus of leukemic B cells but not in
normal B lymphocytes. This nuclear localization could not be observed following BCR triggering. In other words, after BCR engagement, we observed a redistribution of HS1 that was no longer detectable in the nucleus of stimulated leukemic cells. The pre-incubation of cells with PP2, a Src kinase inhibitor, prevents the IgM-mediated redistribution of HS1; so the disappearance of nuclear HS1 is attributable to Src kinases that act at some level of the signal cascade. Since HS1 can interact with actin through the Arp 2/3 complex we performed additional experiments to investigate whether HS1 could interact with cytoskeletal components. We observed that cytosolic HS1 co-localizes with ß-actin both in normal and leukemic B cells. Moreover, for the first time, we demonstrated that in B-CLL,
but not in normal B cells, HS1 co-localizes with ?-tubulin and, in particular, with the centrosome, suggesting that this protein could play a role in the cytoskeletal reorganization of leukemic B cells.
All these findings seem to suggest a pivotal role for HS1 in the regulation of cell survival of leukemic B cells and hint that this protein might represent a target for the development of new therapeutic approaches.

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Tipo di EPrint:Tesi di dottorato
Relatore:Semenzato, Gianpietro
Correlatore:Trentin, Livio
Dottorato (corsi e scuole):Ciclo 20 > Corsi per il 20simo ciclo > ONCOLOGIA E ONCOLOGIA CHIRURGICA
Data di deposito della tesi:31 Gennaio 2008
Anno di Pubblicazione:31 Gennaio 2008
Parole chiave (italiano / inglese):leucemia linfatica cronica; proteina HS1; apoptosi; chemioterapia; citoscheletro
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/15 Malattie del sangue
Struttura di riferimento:Dipartimenti > Dipartimento di Medicina Clinica e Sperimentale
Codice ID:564
Depositato il:11 Nov 2008
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1. Herrinton L.J.: Epidemiology of the Revised European-American Lymphoma Classification subtypes. Epidemiol. Rev., 20:187-203 (1998). Cerca con Google

2. Weiss N.S.: Geographical variation in the incidence of the leukemias and lymphomas. Natl. Cancer Inst. Monogr., 53:139-142 (1979). Cerca con Google

3. Boggs D.R., Chen S.C., Zhang Z.N. and Zhang A.: Chronic lymphocytic leukemia in China. Am. J. Hematol., 25:349-354 (1987). Cerca con Google

4. Yuille M.R., Matutes E., Marossy A., Hilditch B., Catovsky D. and Houlston R.S.: Familial chronic lymphocytic leukaemia: a survey and review of published studies. Br. J. Haematol., 109:794-799 (2000). Cerca con Google

5. Capalbo S., Trerotoli P., Ciancio A., Battista C., Serio G. and Liso V.: Increased risk of lymphoproliferative disorders in relatives of patients with Bcell chronic lymphocytic leukaemia: relevance of the degree of familial linkage. Eur. J. Haematol., 65:114-117 (2000). Cerca con Google

6. Wiernik P.H., Ashwin M., Hu X.P., Paietta E. and Brown K.: Anticipation in familial chronic lymphocytic leukaemia. Br. J. Haematol., 113:407-414 (2001). Cerca con Google

7. Caligaris-Cappio F. and Hamblin T.J.: B-cell chronic lymphocytic leukaemia: a bird of different feather. J. Clin. Oncol., 17:399-408 (1999). Cerca con Google

8. Ward J.H.: Autoimmunity in chronic lymphocytic leukaemia. Curr. Treat. Options Oncol., 2:253-257 (2001). Cerca con Google

9. Dhiel L.F. and Ketchum L.H.: Autoimmune disease and chronic lymphocytic leukaemia: autoimmune haemolytic anemia, pure red cell aplasia and autommune thrombocytopenia. Semin. Oncol., 25:80-85 (1998). Cerca con Google

10. Cheson B.D., Bennett J.M., Grever M., Kay N., Keating M.J., O'Brien S. and Rai K.R.: National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood, 87:4990-4997 (1996). Cerca con Google

11. 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.: Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells. J. Exp. Med., 194:1625-1638 (2001). Cerca con Google

12. Chiorazzi N. and Ferrarini M.: B cell chronic lymphocytic leukemia: lessons learned from studies of the B cell antigen receptor. Annu. Rev. Immunol., 21:841-894 (2003). Cerca con Google

13. Stevenson F.K. and Caligaris-Cappio F.: Chronic lymphocytic leukemia: revelations from the B-cell receptor. Blood, 103:4389-4395 (2004). Cerca con Google

14. Ghia P. and Caligaris-Cappio F.: The indispensable role of microenvironment in the natural history of low-grade B-cell neoplasms. Adv. Cancer Res., 79:157- 173 (2000). Cerca con Google

15. Collins R.J., Verschuer L.A., Harmon B.V., Prentice R.L., Pope J.H. and Kerr J.F. : Spontaneous programmed death (apoptosis) of B-chronic lymphocytic leukaemia cells following their culture in vitro. Br. J. Haematol., 71:343-350 (1989). Cerca con Google

16. Packham G. and Stevenson F.K.: Bodyguards and assassins: Bcl-2 family proteins and apoptosis control in chronic lymphocytic leukaemia. Immunology, 114: 441-449 (2005). Cerca con Google

17. Saxena A., Viswanathan S., Moshynska O., Tandon P., Sankaran K. and Sheridan D.P.: Mcl-1 and Bcl-2/Bax ratio are associated with treatment response but not with Rai stage in B-cell chronic lymphocytic leukemia. Am. J. Hematol. 75: 22-33 (2004). Cerca con Google

18. Niiro H., Clark E.A.: Regulation of B-cell fate by antigen-receptor signals. Nat. Rev. Immunol. 2: 945-956 (2002). Cerca con Google

19. Reth M. and Wienands J.: Initiation and processing of signals from the B cell antigen receptor. Annu. Rev. Immunol. 15: 453-479 (1997). Cerca con Google

20. Alfarano A., Indraccolo S., Circosta P., Minuzzo S., Vallario A., Zamarchi R., Fregonese A., Calderazzo F., Faldella A., Aragno M., Camaschella C., Amadori A.and Caligaris-Cappio F.: An alternatively spliced form of CD79b gene may account for altered B-cell receptor expression in B-chronic lymphocytic leukemia. Blood, 93:2327-2335 (1999). Cerca con Google

21. Cragg M.S., Chan H.T.C., Fox M.D., Tutt A., Smith A., Oscier D.G., Hamblin T.J. and Glennie M.J.: The alternative transcript of CD79b is overexpressed in B-CLL and inhibits signalling for apoptosis. Blood, 100:3068-3076 (2002). Cerca con Google

22. Gupta N. and DeFranco A.L.: Visualizing lipid rafts dynamics and early signalling events durino antigen receptor-ediated B-lymphocyte activation. Mol. Biol. Cell., 14:432-444 (2003). Cerca con Google

23. DeFranco A.L., Chan V.W. and Lowell C.A.: Positive and negative roles of the tyrosie kinase Lyn in B cell function. Semin. Immunol., 10:299-307 (1998). Cerca con Google

24. Mlinaric-Rascan I. and Yamamoto T.: B cell receptor signaling involves physical and functional association of FAK with Lyn and IgM. FEBS Lett., 498:26-31 (2001). Cerca con Google

25. Contri A., Brunati A.M., Trentin L., Cabrelle A., Miorin M., Cesaro L., Pinna L.A., Zambello R., Semenzato G. and Donella-Deana A.: Chronic lymphocytic leukemia B cells contain anomalous Lyn tyrosine kinase, a putative contribution to defective apoptosis. J. Clin. Invest.,115: 369-378 (2005). Cerca con Google

26. Egashira M., Kitamura D., Watanabe T. and Niikawa N.: The human HCLS1 gene maps to chromosome 3q13 by fluorescence in situ hybridization. Cytogenetic Cell Genet., 72:175-6 (1996). Cerca con Google

27. Niiro H. and Clark E.A.: Regulation of B-cell fate by antigen-receptor signals. Nature Rev. Immunol., 2:945-956 (2002). Cerca con Google

28. Sproul T.W., Malapati S., Kim J. and Pierce S.K.: Cutting edge: B cell antigen receptor signaling occurs outside lipid rafts in immature B cells. J. Immunol. 165:6020-6023 (2000). Cerca con Google

29. Weitnraub B.C., Jun J.E., Bishop A.C., Shokat K.M., Thomas M.L., Goodnow C.C.: Entry of B cell receptor into signalling domains is inhibited in tolerant B cells. J. Exp. Med., 191:1443-1448 (2000). Cerca con Google

30. Caligaris-Cappio F.: Role of the microenvironment in chronic lymphocytic leuckamia. Br. J. Haematol., 123:380-383 (2003). Cerca con Google

31. Trentin L., Zambello R., Agostini C., Siviero F., Adami F., Marcolongo R., Raimondi R., Chisesi T., Pizzolo G. and Semenzato G.: Expression and functional role of tumor necrosis factor receptors on leukemc cells frompatients with type B chronic lymphoproliferative disorders. Blood, 81:752-758 (1993). Cerca con Google

32. Trentin L., Cabrelle A., Facco M., Carollo D., Miorin M., Tosoni A., Pizzo P., Binotto G., Nicolardi L., Zambello R., Adami F., Agostini C. and Semenzato G.: Homeostatic chemokines drive migration of malignant B cells in patients with Non-Hodgkin’s Lymphomas. Blood, 104:502-508 (2004). Cerca con Google

33. Richardson S.J., Matthews C., Catherwood M.A., Alexander H.D., Carey B. S., Farrugia J., Gardiner A., Mould S., Oscier D., Copplestone J.A. and Prentice A.G.: ZAP-70 expression is associated with enhanced ability to respond to migratory and survival signals in B-cell chronic lymphocytic leukemia (BCLL). Blood, 107:3584-3592 (2006). Cerca con Google

34. Trentin L., Agostini C., Facco M., Piazza F., Perina A., Siviero M., Gurrieri C., Galvan S., Adami F., Zambello R. and Semenzato G.: The chemokine receptor CXCR3 is expressed on malignant B cells and mediates chemotaxis. J. Clin. Invest., 104:115-121 (1999). Cerca con Google

35. Luo C., Pan H., Mines M., Watson K., Zhang J. and Fan G.H.: CXCL12 induces tyrosine phophorilation of cortactin, which plays a role in CXC chemokine receptor 4-mediated extracellular signal-regulated kinase activation and chemotaxis. J. Biol. Chem., 281:30081-30093 (2006). Cerca con Google

36. Rai K.R. and Han T.: Prognostic factors and clinical staging in chronic lymphocytic leukemia. Hematol. Oncol. Clin. North. Am., 4:447-456 (1990). Cerca con Google

37. Rai K.R., Sawitsky A., Cronkite E.P., Chanana A.D., Levy R.N. and Pasternack B.S.: Clinical staging of chronic lymphocytic leukemia. Blood, 46:219-234 (1975). Cerca con Google

38. Binet J.L., Auquier A., Dighiero G., Chastang C., Piguet H., Goasguen J., Vaugier G., Potron G., Colona P., Oberling F., Thomas M., Tchernia G., Jacquillat C., Boivin P., Lesty C., Duault M.T., Monconduit M., Belabbes S. and Gremy F.: A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer, 48:198-206 (1981). Cerca con Google

39. Montserrat E.: Classical and new prognostic factors in chronic lymphocytic leukemia: where to now? Hematol. J., 3:7-9 (2002). Cerca con Google

40. Mauro F.R., De Rossi G., Burgio V.L., Caruso R., Giannarelli D., Monarca B., Romani C., Baroni C.D. and Mandelli F.: Prognostic value of bone marrow histology in chronic lymphocytic leukemia. A study of 335 untreated cases from a single institution. Haematologica, 79:334-341 (1994). Cerca con Google

41. Melo J.V., Catovsky D., Gregory W.M. and Galton D.A.: The relationship between chronic lymphocytic leukaemia and prolymphocytic leukaemia. IV. Analysis of survival and prognostic features. Br. J. Haematol., 65:23-29 (1987). Cerca con Google

42. Keating M.J.: Chronic lymphocytic leukemia. Semin. Oncol., 26:107-114 (1999). Cerca con Google

43. Hallek M., Langenmayer I., Nerl C., Knauf W., Dietzfelbinger H., Adorf D., Ostwald M., Busch R., Kuhn-Hallek I., Thiel E. and Emmerich B.: Elevated serum thymidine kinase levels identify a subgroup at high risk of disease progression in early, nonsmoldering chronic lymphocytic leukemia. Blood, 93:1732-1737 (1999). Cerca con Google

44. Sarfati M., Chevret S., Chastang C., Biron G., Stryckmans P., Delespesse G., Binet J.L., Merle-Beral H. and Bron D.: Prognostic importance of serum soluble CD23 level in chronic lymphocytic leukemia. Blood, 88:4259-4264 (1996). Cerca con Google

45. Vinante F., Vassanelli A., Zanotti R., Nadali G., Krampera M., Vincenzi C., Morosato L., Chilosi M. and Pizzolo G.: Circulating levels of soluble CD23 reflect clinical and biological features of leukemic B-cell chronic lymphoproliferative disorders. Int. J. Clin. Lab. Res., 25:189-194 (1995). Cerca con Google

46. Hamblin T.J., Davis Z., Gardiner A., Oscier D.G. and Stevenson F.K.: Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood, 94:1848-1854 (1999). Cerca con Google

47. Damle R.N., Wasil T., Fais F., Ghiotto F., Valetto A., Allen S.L., Buchbinder A., Budman D., Dittmar K., Kolitz J., Lichtman S.M., Schulman P., Vinciguerra V.P., Rai K.R., Ferrarini M. and Chiorazzi N.: Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood, 94:1840-1847 (1999). Cerca con Google

48. Tobin G., Thunberg U., Johnson A., Thorn I., Soderberg O., Hultdin M., Botling J., Enblad G., Sallstrom J., Sundstrom C., Roos G. and Rosenquist R.: Somatically mutated Ig V(H)3-21 genes characterize a new subset of chronic lymphocytic leukemia. Blood, 99:2262-2264 (2002). Cerca con Google

49. Ghia P., Stamatopoulos K., Belessi C., Moreno C., Stella S., Guida G., Michel A., Crespo M., Laoutaris N., Montserrat E., Anagnostopoulos A., Dighiero G., Fassas A., Caligaris-Cappio F. and Davi F.: Geographic patterns and pathogenetic implications of IGHV gene usage in chronic lymphocytic leukemia: the lesson of the IGHV3-21 gene. Blood, 105:1678-1685 (2005). Cerca con Google

50. Falt S., Merup M., Tobin G., Thunberg U., Gahrton G., Rosenquist R. and Wennborg A.: Distinctive gene expression pattern in VH3-21 utilizing B-cell chronic lymphocytic leukemia. Blood, 106:681-689 (2005). Cerca con Google

51. Ibrahim S, Keating M, Do KA, O'Brien S, Huh YO, Jilani I, Lerner S, Kantarjian HM and Albitar M: CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia. Blood, 98:181-186 (2001). Cerca con Google

52. Ghia P., Guida G., Stella S., Gottardi D., Geuna M., Strola G., Scielzo C. and Caligaris-Cappio F.: The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression. Cerca con Google

Blood, 101:1262-1269 (2003). Cerca con Google

53. Hamblin T.J., Orchard J.A., Ibbotson R.E., Davis Z., Thomas P.W., Stevenson F.K. and Oscier D.G.: CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease. Blood, 99:1023-1029 (2002). Cerca con Google

54. Ghia P., Guida G., Scielzo C., Geuna M. and Caligaris-Cappio F.: CD38 modifications in chronic lymphocytic leukemia: are they relevant? Leukemia, 18:1733-1735. (2004). Cerca con Google

55. Rosenwald A., Alizadeh A.A., Widhopf G., Simon R., Davis R.E., Yu X., Yang L., Pickeral O.K., Rassenti L.Z., Powell J., Botstein D., Byrd J.C., Grever M.R., Cheson B.D., Chiorazzi N., Wilson W.H., Kipps T.J., Brown P.O. and Staudt L.M.: Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J. Exp. Med., Cerca con Google

194:1639-1647 (2001). Cerca con Google

56. Wiestner A., Rosenwald A., Barry T.S., Wright G., Davis R.E., Henrickson S.E., Zhao H., Ibbotson R.E., Orchard J.A., Davis Z., Stetler-Stevenson M., Raffeld M., Arthur D.C., Marti G.E., Wilson W.H., Hamblin T.J., Oscier D.G. and Staudt L.M.: ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood, 101:4944-4951 (2003). Cerca con Google

57. Rassenti L.Z., Huynh L., Toy T.L., Chen L., Keating M.J., Gribben J.G., Neuberg D.S., Flinn I.W., Rai K.R., Byrd J.C., Kay N.E., Greaves A., Weiss A. and Kipps T.J.: ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N. Engl. J. Med., 351:893-901 (2004). Cerca con Google

58. Crespo M., Bosch F., Villamor N., Bellosillo B., Colomer D., Rozman M., Marce S., Lopez-Guillermo A., Campo E. and Montserrat E.: ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N. Engl. J. Med., 348:1764-1775 (2003). Cerca con Google

59. Krober A., Bloehdorn J., Hafner S., Buhler A., Seiler T., Kienle D., Winkler D., Bangerter M., Schlenk R.F., Benner A., Lichter P., Dohner H. and Stilgenbauer S.: Additional genetic high-risk features such as 11q deletion, 17p deletion, and V3-21 usage characterize discordance of ZAP-70 and VH mutation status in chronic lymphocytic leukemia. J. Clin. Oncol., 24:969-975 (2006). Cerca con Google

60. Del Giudice I., Morilla A., Osuji N., Matutes E., Morilla R., Burford A., Maravelaki S., Owusu-Ankomah K., Swansbury J., A'Hern R., Brito-Babapulle V. and Catovsky D.: Zeta-chain associated protein 70 and CD38 combined predict the time to first treatment in patients with chronic lymphocytic leukemia. Cancer, 104:2124-2132 (2005). Cerca con Google

61. Dohner H., Stilgenbauer S., Benner A., Leupolt E., Krober A., Bullinger L., Dohner K., Bentz M. and Lichter P.: Genomic aberrations and survival in chronic lymphocytic leukemia. N. Engl. J. Med., 343:1910-1916 (2000). Cerca con Google

62. Grever M.R., Lucas D.M., Dewald G.W., Neuberg D.S., Reed J.C., Kitada S., Flinn I.W., Tallman M.S., Appelbaum F.R., Larson R.A., Paietta E., Jelinek D.F., Gribben J.G. and Byrd J.C.: Comprehensive assessment of genetic and Cerca con Google

molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the US Intergroup Phase III Trial E2997. J. Clin. Oncol., 25:799-804 (2007). Cerca con Google

63. Krober A., Seiler T., Benner A., Bullinger L., Bruckle E., Lichter P., Dohner H. and Stilgenbauer S.: V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood, 100:1410- 1416 (2002). Cerca con Google

64. Oscier D.G., Gardiner A.C., Mould S.J., Glide S., Davis Z.A., Ibbotson R.E., Corcoran M.M., Chapman R.M., Thomas P.W., Copplestone J.A., Orchard J.A. and Hamblin T.J.: Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors. Blood, 100:1177-1184 (2002). Cerca con Google

65. Terrin L., Trentin L., Degan M., Corradini I., Bertorelle R., Carli P., Maschio N., Bo M.D., Noventa F., Gattei V., Semenzato G. and De Rossi A.: Telomerase expression in B-cell chronic lymphocytic leukemia predicts survival and delineates subgroups of patients with the same igVH mutation status and different outcome. Leukemia, 21:965-972 (2007). Cerca con Google

66. Ricca I., Rocci A., Drandi D., Francese R., Compagno M., Lobetti Bodoni C., De Marco F., Astolfi M., Monitillo L., Vallet S., Calvi R., Ficara F., Omede P., Rosato R., Gallamini A., Marinone C., Bergui L., Boccadoro M., Tarella C. and Ladetto M.: Telomere length identifies two different prognostic subgroups among VH-unmutated B-cell chronic lymphocytic leukemia patients. Leukemia, 21:697-705 (2007). Cerca con Google

67. Binet J.L., Caligaris-Cappio F., Catovsky D., Cheson B., Davis T., Dighiero G., Dohner H., Hallek M., Hillmen P., Keating M., Montserrat E., Kipps T.J. and Rai K.: Perspectives on the use of new diagnostic tools in the treatment of chronic lymphocytic leukemia. Blood, 107:859-861 (2006). Cerca con Google

68. Cheson B.D., Bennett J.M., Grever M., Kay N., Keating M.J., O'Brien S. and Rai K.R.: National Cancer Institute-sponsored Working Group guidelines forchronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood, 87:4990-4997 (1996). Cerca con Google

69. Dighiero G., Maloum K., Desablens B., Cazin B., Navarro M., Leblay R., Leporrier M., Jaubert J., Lepeu G., Dreyfus B., Binet J.L. and Travade P.: Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia. N. Engl. J. Med., 338:1506-1514 (1998). Cerca con Google

70. The French Cooperative Group on Chronic Lymphocytic Leukemia: A randomized clinical trial of chlorambucil versus COP in stage B chronic lymphocytic leukemia. Blood, 75:1422-1425 (1990). Cerca con Google

71. Jaksic B., Brugiatelli M., Krc I., Losonczi H., Holowiecki J., Planinc-Peraica A., Kusec R., Morabito F., Iacopino P. and Lutz D.: High dose chlorambucil versus Binet's modified cyclophosphamide, doxorubicin, vincristine, and prednisone regimen in the treatment of patients with advanced B-cell chronic lymphocytic leukemia. Results of an international multicenter randomized trial. International Society for Chemo-Immunotherapy, Vienna. Cancer, 79:2107- 2114 (1997). Cerca con Google

72. Keating M.J., O'Brien S., Lerner S., Koller C., Beran M., Robertson L.E., Freireich E.J., Estey E. and Kantarjian H.: Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as initial therapy. Blood, 92:1165-1171 (1998). Cerca con Google

73. Rai K.R., Peterson B.L., Appelbaum F.R., Kolitz J., Elias L., Shepherd L., Hines J., Threatte G.A., Larson R.A., Cheson B.D. and Schiffer C.A.: Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N. Engl. J. Med., 343:1750-1757 (2000). Cerca con Google

74. Leporrier M., Chevret S., Cazin B., Boudjerra N., Feugier P., Desablens B., Rapp M.J., Jaubert J., Autrand C., Divine M., Dreyfus B., Maloum K., Travade P., Dighiero G., Binet J.L. and Chastang C.: Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients. Blood, 98:2319-2325 (2001). Cerca con Google

75. Dillman R.O., Mick R. and McIntyre O.R.: Pentostatin in chronic lymphocytic leukemia: a phase II trial of Cancer and Leukemia group B. J. Clin. Oncol., 7:433-438 (1989). Cerca con Google

76. Robak T., Blonski J.Z., Kasznicki M., Gora-Tybor I., Dwilewicz-Trojaczek J., Boguradzki P., Konopka L., Ceglarek B., Sulek J., Kuliczkowski K., Wolowiec D., Stella-Holowiecka B., Skotnicki A.B., Nowak W., Moskwa-Sroka B., Dmoszynska A. and Calbecka M.: Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia. Leukemia, 15:1510-1516 (2001). Cerca con Google

77. Yamauchi T., Nowak B.J., Keating M.J. and Plunkett W.: DNA repair initiated in chronic lymphocytic leukemia lymphocytes by 4- hydroperoxycyclophosphamide is inhibited by fludarabine and clofarabine. Clin. Cancer Res., 7:3580-3589 (2001). Cerca con Google

78. Flinn I.W., Neuberg D.S., Grever M.R., Dewald G.W., Bennett J.M., Paietta E.M., Hussein M.A., Appelbaum F.R., Larson R.A., Moore D.F. Jr and Tallman M.S.: Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. J. Clin. Oncol., 25:793-798 (2007). Cerca con Google

79. Demidem A., Lam T., Alas S., Hariharan K., Hanna N. and Bonavida B.: Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. Cancer Biother. Radiopharm., 12:177-186 (1997). Cerca con Google

80. Alas S., Emmanouilides C. and Bonavida B.: Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis. Clin. Cancer Res., 7:709-723 (2001). Cerca con Google

81. Di Gaetano N., Xiao Y., Erba E., Bassan R., Rambaldi A., Golay J. and Introna M.: Synergism between fludarabine and rituximab revealed in a follicular lymphoma cell line resistant to the cytotoxic activity of either drug alone. Br. J. Haematol., 114:800-809 (2001). Cerca con Google

82. Wierda W., O'Brien S., Wen S., Faderl S., Garcia-Manero G., Thomas D., Do K.A., Cortes J., Koller C., Beran M., Ferrajoli A., Giles F., Lerner S., Albitar M., Kantarjian H. and Keating M.: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J. Clin. Oncol., 23:4070-4078 (2005). Cerca con Google

83. Keating M.J., O'Brien S., Albitar M., Lerner S., Plunkett W., Giles F., Andreeff M., Cortes J., Faderl S., Thomas D., Koller C., Wierda W., Detry M.A., Lynn A. and Kantarjian H.: Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J. Clin. Oncol., 23:4079-4088 (2005). Cerca con Google

84. Montillo M., Cafro A.M., Tedeschi A., Brando B., Oreste P., Veronese S., Rossi V., Cairoli R., Pungolino E. and Morra E.: Safety and efficacy of subcutaneous Campath-1H for treating residual disease in patients with chronic lymphocytic leukemia responding to fludarabine. Haematologica, 87:695-700 (2002). Cerca con Google

85. Stilgenbauer S. and Dohner H.: Campath-1H-induced complete remission of chronic lymphocytic leukemia despite p53 gene mutation and resistance to chemotherapy. N. Engl. J. Med., 347:452-453 (2002). Cerca con Google

86. O'Brien S., Moore J.O., Boyd T.E., Larratt L.M., Skotnicki A., Koziner B., Chanan-Khan A.A., Seymour J.F., Bociek R.G., Pavletic S. and Rai K.R.: Randomized phase III trial of fludarabine plus cyclophosphamide with or without oblimersen sodium (Bcl-2 antisense) in patients with relapsed or refractory chronic lymphocytic leukemia. J. Clin. Oncol., 25:1114-1120 (2007). Cerca con Google

87. Moreno C., Villamor N., Colomer D., Esteve J., Martino R., Nomdedeu J., Bosch F., Lopez-Guillermo A., Campo E., Sierra J. and Montserrat E.: Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia. J. Clin. Oncol., 23:3433-3438 (2005). Cerca con Google

88. Dreger P. and Montserrat E.: Autologous and allogeneic stem cell transplantation for chronic lymphocytic leukemia. Leukemia, 16:985-992 (2002). Cerca con Google

89. Kitamura D., Kaneko H., Miyagoe Y., Ariyasu T. and Watanabe T.: Isolation and characterization of a novel human gene expressed specifically in the cells of hematopoietic lineage. Nucleic Acids Research, 17: 9367-9379 (1989). Cerca con Google

90. Fischer U., Michel A. and Meese E.U.: Expression of the gene for hematopoietic cell specific protein is not restricted to cells of hematopoietic origin. Int. J. Mol. Med., 15: 611-615 (2005). Cerca con Google

91. GSH van Rossum A., Schuuring-Scholtes E., van Buuren-van Seggelen V., Kluin P.M. and Schuuring E.: Comparative genome analysis of cortactin and HS1: the significance of the F-actin binding repeat domain. BMC Genomics, 6:1-14 (2005). Cerca con Google

92. Hao J.J., Zhu J., Zhou K., Smith N. and Zhan X.: The Coiled-coil Domain Is Required for HS1 to Bind to F-actin and Activate Arp2/3 Complex. J. Biol. Chem., 280: 37988-37994 (2005). Cerca con Google

93. Suzuki Y., Demoliere C., Kitamura D., Takeshita H., Deuschle U. and Watanabe T.: HAX-1, a Novel Intracellular Protein, Localized on Mitochondria, Directly Associates with HS1, a Substrate of Src Family Tyrosine Kinases. J. Immunol., 158: 2736-2744 (1997). Cerca con Google

94. Cilenti L., Soundarapandian M.M., Kyriazis G.A., Stratico V., Singh S., Gupta S., Bonventre J.V., Alnemri E.S. and Zervos A.S.: Regulation of HAX-1 Antiapoptotic Protein by Omi/HtrA2 Protease during Cell Death. J. Biol. Chem., 279: 50295-50301 (2004). Cerca con Google

95. Brunati A.M., Deana R., Folda A., Massimino M.L., Marin O., Ledro S., Pinna L.A. and Donella-Deana A.: Thrombin-induced Tyrosine Phosphorylation of HS1 in Human Platelets Is Sequentially Catalyzed by Syk and Lyn Tyrosine Kinases and Associated with the Cellular Migration of the Protein. J. Biol. Chem., 280: 21029-21035 (2005). Cerca con Google

96. Yamanashi Y., Okada M., Semba T., Yamori T., Umemori H., Tsunasawa S., Toyoshima K., Kitamura D., Watanabe T. and Yamamoto T.: Identification of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling. Immunology, 90:3631-3635 (1993). Cerca con Google

97. Ruzzene M., Brunati A.M., Marin O., Donella-Deana A. and Pinna L.A.: SH2 Domains Mediate the Sequential Phosphorylation of HS1 Protein by p72syk and Src-Related Protein Tyrosine Kinases. Biochemistry, 35:5327-5332 (1996). Cerca con Google

98. Brunati A.M., Donella-Deana A., James P., Quadroni M., Contri A., Marin O. and Pinna L.A.: Molecular Features Underlying the Sequential Phosphorylation of HS1 Protein and Its Association with c-Fgr Protein-tyrosine Kinase. J. Biol. Chem., 274:7557-7564 (1999). Cerca con Google

99. Brunati A.M., Bordin L., Clari G., James P., Quadroni M., Baritono E., Pinna L.A. and Donella-Deana A.: Sequential phosphorylation of protein band 3 by Syk and Lyn tyrosine kinases in intact human erythrocytes: identification of primary and secondary phosphorylation sites. Blood, 96: 1550-1557 (2000). Cerca con Google

100. Taniuchi I., Kitamura D., Maekawa Y., Fukuda T., Kishi H. and Watanabe T.: Antigen-receptor induced clonal expansion and deletion of lymphocytes are impaired in mice lacking HS1 protein, a substrate of the antigen-receptorcoupledtyrosine kinases. The EMBO Journal, 14:3664-3678 (1995). Cerca con Google

101. Fukuda T., Kitamura D., Taniuchi I., Maekawa Y., Benhamou L.E., Sarthou P. and Watanabe T.: Restoration of surface IgM-mediated apoptosis in an anti- IgM-resistant variant of WEHI-231 lymphoma cells By HS1, a protein-tyrosine kinase substrate. Immunology, 92:7302-7306 (1995). Cerca con Google

102. Scielzo C., Ghia P., Conti A., Bachi A., Guida G., Geuna M., Alessio M. and Caligaris-Cappio F.: HS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor prognoses. J. Clin. Invest., 115:1644-1650 (2005). Cerca con Google

103. Ruzzene M., Penzo D. and Pinna L.A.: Protein kinase CK2 inhibitor 4,5,6,7- tetrabromobenzotriazole (TBB) induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells. Biochem. J., 364: 41-47 (2002). Cerca con Google

104. Chen Y., Kori R., John B. and Tan T.: Caspase-Mediated Cleavage of Actin- Binding and SH3-Domain-Containing Proteins Cortactin, HS1, and HIP-55 during Apoptosis. Bioch. Bioph. Res. Com., 288:981-989 (2001). Cerca con Google

105. Muzio M., Scielzo C., Frenquelli M., Bachi A., De Palma M., Alessio M., Ghia P. and Caligaris-Cappio F.: HS1 complexes with cytoskeleton adapters in normal and malignant chronic lymphocytic leukemia B cells. Leukemia, 21:2067-2070 (2007). Cerca con Google

106. Gomez T.S., McCarney S.D., Carrizosa E., Labno C.M., Comiskey E.O., Nolz J.C., Zhu P., Freedman B.D., Clark M.R., Rawlings D.J., Billadeau D.D. and Burkhardt J.K.: HS1 Functions as an Essential Actin-Regulatory Adaptor Protein at the Immune Synapse. Immunity, 24:741-752 (2006). Cerca con Google

107. Billadeau D.D. and Burkhardt J.K.: Regulation of Cytoskeletal Dynamics at the Immune Synapse: New Stars Join the Actin Troupe. Traffic, 7:1451-1460 (2006). Cerca con Google

108. Tachibana H., Koga K., Fujimura Y. and Yamada K.: A receptor for green tea polyphenol EGCG. Nature structural and molecular biology, 11:380-381 (2004). Cerca con Google

109. Yamanashi B.Y., Fukuda T., Nishizumi H., Inazu T., Higashi K., Kitamura D., Ishida T., Yamamura H., Watanabe T. and Yamamoto T.: Role of tyrosine phosphorylation of HS1 in B cell antigen receptor-mediated apoptosis. J.Exp Med., 185:1387-1392 (1997). Cerca con Google

110. He H., Watanabe T., Zhan X., Huang C., Schuuring E., Fukami K., Takenawa T., Kumar C., Simpson R.J. and Maruta H.: Role of phosphatidylinositol 4,5- bisphosphate in Ras/Rac-induced disruption of the cortactin-actomyosin II complex and malignant transformation. Mol. Cell. Biol., 18:3829-3837 (1998). Cerca con Google

111. Azimzadeh J. and Bornens M.: Structure and duplication of the centrosome. J. Cell. Sci., 120:2139-2142 (2007). Cerca con Google

112. Nigg E.A.: Origins and consequences of centrosome aberrations in human cancers. Int. J. Cancer., 119:2717-2723 (2006). Cerca con Google

113. Chiorazzi N.: Cell proliferation and death: forgotten features of chronic lymphocytic leukemia B cells. Best Pract. Res. Clin. Hematol., 20:399-413 (2007). Cerca con Google

114. Hensel M., Zoz M., Giesecke C., Benner A., Neben K., Jauch A., Stilgenbauer S., Ho A.D. and Krämer A.: High rate of centrosome aberrations and correlation with proliferative activity in patients with untreated B-cell chronic lymphocytic leukemia. Int. J. Cancer., 121:978-83 (2007). Cerca con Google

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