Haematologica 2004;89: supplement no. 6 - Supplements ...

More documents

Recommendations

Info

164PostersPO-168TLR7 AND TLR9 LIGANDS EXHIBIT IMMUNOSTIMULATORYACTIVITIES ON CHRONIC LYMPHOCYTIC LEUKEMIA B CELLSFilì L,* Brugnolo F,* Sampognaro S,* Liotta F,* CosmiL,* Manuelli C, # Santini V, § Ciolli S, § Bosi A, § MaggiE,* Romagnani S,* Annunziato F,* Parronchi P**Dept of Internal Medicine, Section of Immunoallergology,# Dept. of Dermatological Sciences and § Dept.of Hematology, University of Florence, ItalyNatural and synthetic Toll-like Receptor (TLR) ligandscan activate cells of the innate immunity andsome of them also show the ability to modulateimmunocompetent cells. In particular, short-lenghtCpG-containing motif oligodeoxynucleotides (CpG-ODNs) can stimulate proliferation and differentiationof murine and human B cells. More recently, imidazoquinolineshave been demonstrated to stimulatenormal human B cells through a TLR7 (and 8)-mediatedsignaling. Chronic lymphocytic leukemia (B-CLL)cells represent a mature malignant counterpart of Bcells characterized by high apoptosis rate in vitro,unresponsiveness to ordinary agents promoting differentiationand proliferation. Limited data are knownon TLR in B-CLL cells. In our study, the analysis ofTLR1-10 by real-time PCR showed that highly purifiedCD5+ B-CLL cells expressed TLR7 and 9 whereasTLR8 and TLR1-5 were negative. We then comparedthe effects of TLR7-ligand R-848 (Resiquimod)with the phosphorothioate CpG ODNs DSP30 and2006 which bind to TLR9.For control, LPS and syntheticdouble strand RNA poly I: poly C were used. R-848 was able to induce a significant proliferation ofCD5+ leukemic B cells in almost all the analyzed B-CLL (90% cases) in a dose-curve manner with a similarrate of proliferation to CpG-ODNs. CFDA-SEanalysis confirmed that CD19+CD5+ cells wereresponsible for thymidine-uptake. The stimulatoryeffect was directed to B cells as the depletion of PDCsdid not affect the proliferative response. More interestingly,R-848 induced a strong up-regulation ofcostimulatory molecule expression (CD40, CD80,CD86) together with increased expression of CD20and MHC class II molecules and R-848 and CpG-ODNpre-incubated B cells also exhibited increased stimulatoryability to allogeneic T cells in MLR even atvery low E:R ratios (1:500). Finally, R-848 and, in amore limited way, CpG-ODNs were able to stimulatethe differentiation of B-CLL cells into actively IgMproducingcells. Taken together, our data indicate thatResiquimod is a potent immunomodulator to inducematuration of neoplastic B cells to stimulate an efficientT cell response in some haematologic malignancies.PO-169HIGH LEVELS OF ACTIVATED CASPASES IDENTIFY PATIENTSWITH INCREASED RISK OF DISEASE PROGRESSION IN B-CELLCHRONIC LYMPHOCYTIC LEUKEMIADel Poeta G, Del Principe MI, Luciano F,Irno Consalvo M, Mazzone C, Suppo G, Marini R,Maurillo L, Venditti A, Buccisano F, Bruno A,Piccioni D, Franchi A, Meoni G, Amadori SCattedra di Ematologia, Università “Tor Vergata”,Ospedale S. Eugenio, Rome, ItalyB-cell chronic lymphocytic leucemia (B-CLL) is adisease characterized by the progressive accumulationof tumor cells which do not proliferate rapidly,but fail to undergo death. Even though almost allperipheral blood B-cells are arrested in G0 phase ofthe cell cycle, a proliferating pool of cells might beinvolved in disease progression. As a matter of fact,increased clonal expansion of leukemic B-CLL cells inprogressive patients might be due to proliferation inexcess of apoptosis. A central component of thisapoptotic machinery is a proteolytic system thatinvolves a family of proteases called caspases. Thesecaspases can be divided into two groups: largeprodomain containing upstream initiators (caspase-8, caspase-9), which may initiate the proteolytic cascade,and small prodomain containing downstreameffectors (caspase-2, caspase-3, caspase-6), which inturn can amplify the signal by cleaving initiator-caspasesand kill the cell by cleaving key intracellulartargets. In order to define the prognostic impact ofthese apoptotic enzymes on the clinical outcome ofB-CLL, we investigated 178 patients, median age 65years, 88 males and 90 females. Activated caspases2, 3, 6, 8 and 9 were determined on cellular cytosolicextracts through a spectrophotometric detectionof the chromophore p-nitroanilide (pNA) after cleavagefrom the labeled substrates (VDVAD for caspase-2, DEVD for caspase-3, VEID for caspase-6, IETD forcaspase-8 and LEHD for caspase-9). The pNA lightemission was quantified using a microplate reader at400-405 nm. Caspases activities were evaluated bythe absorbance ratio samples/background readings(O. D. ). A mean value of all caspases activities (2, 3,6, 8 and 9) was calculated for each B-CLL patient. Thethreshold of positivity was set at > 0.082 O. D. medianvalue. With regard to patients characteristics, 53had low Rai stage, 120 intermediate stage and 5 highstage. No significant correlations were foundbetween modified Rai stages or β2-microglobulin andcaspases activity levels. On the other hand, there wasa very significant association between high caspasesactivity levels and lymphocyte doubling time (LDT)
VIII Congress of the Italian Society of Experimental Hematology, Pavia, September 14-16, 2004165caspases activity and high bcl-2 levels (p=0.05).Finally, there was only a trend of association betweenlow ZAP-70 or CD38 levels and low caspases activity(p=0.1, not significant). With regard the clinicaloutcome, impressive shorter progression-free survival(PFS) and overall survival (OS) were observed inpatients with higher caspases activity levels (18% vs93% at 9 years; p
Page 1 and 2:
haematologicahJournal of Hematology
Page 3:
haematologicaeditorial boardeditor-
Page 6:
supplement 6, September 2004Table o
Page 9 and 10:
VIII Congress of the Italian Societ
Page 11 and 12:
Page 13 and 14:
Page 15 and 16:
Page 18 and 19:
12Main ProgramAcknowledgments: this
Page 20 and 21:
14Main Programhaematologica vol. 89
Page 22 and 23:
16Oral Communicationsexpression. TR
Page 24 and 25:
18Oral CommunicationsBEST-06NK CELL
Page 26 and 27:
20Oral Communications: Molecular He
Page 28 and 29:
22Oral Communications: Molecular He
Page 30 and 31:
24Oral Communications: Hematopoieti
Page 32 and 33:
Page 34 and 35:
Page 36 and 37:
30Oral Communications: Non-malignan
Page 38 and 39:
32Oral Communicationsmodulation of
Page 40 and 41:
34Oral Communicationsfollow-up samp
Page 42 and 43:
36Oral Communicationsinary results
Page 44 and 45:
38Oral Communicationslow-grade NHL)
Page 46 and 47:
40Oral CommunicationsOral Communica
Page 48 and 49:
42Oral Communicationsboth increased
Page 50 and 51:
44Oral CommunicationsCO-40POTENTIAL
Page 52 and 53:
46Oral Communicationsshowed an exte
Page 54 and 55:
48Oral CommunicationsThe molecular
Page 56 and 57:
50Oral Communicationsthe transcript
Page 58 and 59:
52Oral Communicationsing to apoptot
Page 60 and 61:
54Oral CommunicationsCO-54NEOPLASTI
Page 62 and 63:
56Oral CommunicationsOral Communica
Page 64 and 65:
58Oral Communicationssystem-Promega
Page 66 and 67:
60Oral Communicationsthe relationsh
Page 68 and 69:
62PostersPosterACUTE MYELOID LEUKEM
Page 70 and 71:
64Postersone course of CI-FLA. Ther
Page 72 and 73:
66Postersed to GST deletions and CY
Page 74 and 75:
68Posterstion until optimal VPA pla
Page 76 and 77:
70Posterseffective biotechnological
Page 78 and 79:
72Postersdirectly to maintenance th
Page 80 and 81:
74PostersPosterACUTE LYMPHOID LEUKE
Page 82 and 83:
76Postersformed in half the patient
Page 84 and 85:
78Posterspatients correlating data
Page 86 and 87:
80Postersleukemia-related and thus
Page 88 and 89:
82PostersCD33/CD16, CD13/CD16, CD45
Page 90 and 91:
84PostersIn myelodysplastic syndrom
Page 92 and 93:
86Postersin our series of 376 conse
Page 94 and 95:
88PostersPO-041FUNCTIONAL ANALYSIS
Page 96 and 97:
90PostersPO-044FISHING NUP98 INVOLV
Page 98 and 99:
92Postersof AML blasts to RA. In su
Page 100 and 101:
94Postersafter 72-96 h treatment wi
Page 102 and 103:
96PostersPosterMOLECULAR HEMATOLOGY
Page 104 and 105:
98Postersanalyse the transcribed HU
Page 106 and 107:
100Postersed with the gain of the i
Page 108 and 109:
102Postershowever, been reported in
Page 110 and 111:
104Postersand the intrinsic apoptot
Page 112 and 113:
106Postersferentation by BM stromal
Page 114 and 115:
108PostersPO-075NONMYELOABLATIVE AL
Page 116 and 117:
110Posters9-12, 17-20/28 d on odd c
Page 118 and 119:
112PostersPosterMULTIPLE MYELOMA II
Page 120 and 121: 114Posterssion, the immunomodulator
Page 122 and 123: 116Posters(p-ERK1/2) levels in myel
Page 124 and 125: 118PostersPO-092ROLE OF THE MEVALON
Page 126 and 127: 120Postershis study evaluates the p
Page 128 and 129: 122PostersPosterNON-ONCOLOGICAL HEM
Page 130 and 131: 124PostersPO-101A WHOLE BLOOD FLOW
Page 132 and 133: 126Postersthat ITP DCs, after pulsi
Page 134 and 135: 128PostersTherefore in the proposit
Page 136 and 137: 130Postersods and early effective a
Page 138 and 139: 132PostersPO-116FIP1L1-PDGFRA FUSIO
Page 140 and 141: 134Postersand of course, as reducti
Page 142 and 143: 136Posterscurrently under study bec
Page 144 and 145: 138Postersmg/day (Haematologica 200
Page 146 and 147: 140Postersno severe reaction were o
Page 148 and 149: 142PostersCML for clinical and haem
Page 150 and 151: 144PostersPO-135THE ATG-SAPORIN-S6
Page 152 and 153: 146Postersthrough a flow cytometry-
Page 154 and 155: 148Posterspredominant TCR peak prec
Page 156 and 157: 150Postersrejection or cytopenia, w
Page 158 and 159: 152Postersphocytes. Anti-leptin blo
Page 160 and 161: 154Postersmy), which the patient re
Page 162 and 163: 156Postersgr/m 2 +GCSF) followed by
Page 164 and 165: 158Postersremission of 100% of MCL
Page 166 and 167: 160Posterswould require an early an
Page 168 and 169: 162PostersPO-165SPONTANEOUS MOBILIZ
Page 172 and 173: 166PostersFR and/or CDR clustering
Page 174 and 175: 168PostersPO-174INDUCTION OF FAS UP
Page 176 and 177: 170Postersup data were available, m
Page 178 and 179: 172Posterssamples showing RFC methy
Page 180 and 181: 174PostersIn the last few years the
Page 182 and 183: 176PostersPO-187RELAPSED/REFRACTORY
Page 184 and 185: 178Posters1.The association of prim
Page 186 and 187: 180Posterswith generalizated lympho
Page 188 and 189: 182PostersPO-196EPRATUZUMAB/SAPORIN
Page 190 and 191: 184Postersantioxidant capacity of p
Page 192 and 193: 186PostersCD16/CD56 + (NK) cells an
Page 194 and 195: 188Postersby PBSCT, as the general
Page 196 and 197: 190Postersnode biopsies, three from
Page 198 and 199: 192PostersPO-212ANALYSIS OF IGV GEN
Page 200 and 201: 194Postershaematologica vol. 89[sup
Page 202 and 203: IIVIII Congress of the Italian Soci
Page 204 and 205: IVVIII Congress of the Italian Soci
Page 206 and 207: VIVIII Congress of the Italian Soci
Page 208 and 209: VIIIVIII Congress of the Italian So
Page 210 and 211: XVIII Congress of the Italian Socie
show all

Haematologica 2004;89: supplement no. 6 - Supplements ...

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?