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XIV Congress of the Italian Society of Experimental Hematology, Rimini Journal of the European Hematology Association Published by the Ferrata Storti Foundation XIV Congress of the Italian Society of Experimental Hematology Rimini, Italy, October 19-21, 2016 haematologicaABSTRACT BOOK ISSN 0390-6078 Volume 101 OCTOBER 2016|s3 XIV Congress of the Italian Society of Experimental Hematology Rimini, Italy, October 19-21, 2016 COMITATO SCIENTIFICO Massimo MASSAIA, Presidente Maria Teresa VOSO, Vice Presidente Roberto Massimo LEMOLI, Past President Barbara CASTELLA Sara GALIMBERTI Nicola GIULIANI Mauro KRAMPERA Luca MALCOVATI Fortunato MORABITO Stefano SACCHI Paolo VIGNERI SEGRETERIA SIES Via Marconi, 36 - 40122 Bologna Tel. 051 6390906 - Fax 051 4219534 E-mail: [email protected] www.siesonline.it SEGRETERIA ORGANIZZATIVA Studio ER Congressi Via Marconi, 36 - 40122 Bologna Tel. 051 4210559 - Fax 051 4210174 E-mail: [email protected] www.ercongressi.it ABSTRACT BOOK XIV Congress of the Italian Society of Experimental Hematology Rimini, Italy, October 19-21, 2016 Contributors JANSSEN BRISTOL-MYERS SQUIBB GILEAD NOVARTIS ONCOLOGY ROCHE ABBVIE CELGENE INCYTE BIOSCIENCES DIASORIN ROCHE DIAGNOSTICS TAKEDA PICCIN WERFEN supplement 3 - October 2016 Table of Contents XIV Congress of the Italian Society of Experimental Hematology Rimini, Italy, October 19-21, 2016 Main Program . 1 Best Abstracts . 12 Oral Communications Session 1. C001-C008 Acute Leukemia 1. 15 Session 2. C009-C016 Monoclonal Gammopathies and Multiple Myeloma 1 . 19 Session 3. C017-C024 Chronic Lymphocytic Leukemia and Chronic Lymphoproliferative Disorders. 23 Session 4. C025-C032 Myeloproliferative Disorders and Chronic Myeloid Leukemia . 27 Session 5. C033-C040 Lymphomas . 32 Session 6. C041-C048 Stem Cells and Growth Factors . 36 Session 7. C049-C056 Immunotherapy and cell therapy. 40 Session 8. C057-C064 Immunophenotyping and Minimal Residual Disease . 43 Session 9. C065-C072 Monoclonal Gammopathies and Multiple Myeloma 2 . 48 Session 10. C073-C080 Acute Leukemia 2. 52 Session 11. C081-C088 Molecular Hematology. 56 Session 12. C089-C096 Myelodysplastic Myeloproliferative Syndromes . 60 Posters Session 1. P001-P012 Acute Leukemia 1. 65 Session 2. P013-P022 Myeloproliferative Disorders and Chronic Myeloid Leukemia 1 . 70 Session 3. P023-P034 Chronic Lymphocytic Leukemia and Chronic Lymphoproliferative Disorders 1 . 76 Session 4. P035-P042 Lymphomas and Multiple Myeloma 1. 82 Session 5. P043-P056 Molecular Hematology. 86 Session 6. P057-P068 Acute Leukemia 2. 93 Session 7. P069-P078 Myeloproliferative Disorders and Chronic Myeloid Leukemia 2 . 100 Session 8. P079-P089 Chronic Lymphocytic Leukemia and Chronic Lymphoproliferative Disorders 2 . 105 Session 9. P090-P097 Lymphomas Multiple Myeloma 2 . 111 Session 10. P098-P113 Stem Cells and Growth Factors . 115 Haematologica 2016; vol. 101; supplement 3 - October 2016 http://www.haematologica.org/ XIV Congress of the Italian Society of Experimental Hematology Rimini, Italy, October 19-21, 2016 MAIN PROGRAM MECHANISMS OF IMMUNOREGULATION OF ACUTE DETECTION OF CHRONIC MYELOID LEUKEMIA STEM CELLS LEUKEMIA BY FLOW-CYTOMETRY R.M. Lemoli M. Bocchia Clinic of Hematology, Department of Internal Medicine (DiMI), Uni- Hematology Unit, University of Siena, Azienda Ospedaliera Universi- versity of Genoa, Genoa, Italy taria Senese, Siena, Italy The initiation and development of acute leukemia is sustained by In chronic myeloid leukemia (CML) data suggest that relapse after an immunosuppressive microenvironment where both innate and tyrosine kinase inhibitors (TKIs) discontinuation is due to the per- adaptive immune responses to cancer cells are profoundly deregu- sistence of leukemic stem cells (LSCs) intrinsically resistant to TKIs. lated. Several immunosuppressive mechanisms are operative result- Survival of CML LSCs may be the consequence of activation of ing in the escape of tumor cells from natural immune control. Thus, several pathways BCR-ABL1 independent. qRT-PCR, the most a better understanding of the mechanisms governing the interplay sensitive assay to monitor disease status in CML patients, may be between the microenvironment and cancer cells is mandatory for inappropriate to quantify resid ual quiescent CML LSCs that are the development of innovative therapies. Indeed, modulation of the transcriptionally silent. In CML, LSC supposedly reside within the immune system by allogeneic stem cell transplantation and cellular CD34+/CD38-/Lin- fraction of the leukemic clone. However, nor- adoptive immunotherapy has dramatically improved the long-term mal hematopoietic SCs also exhibit this phenotype so that addi- outcome of many patients whereas the targeting of specific tional markers are required to discriminate CML LSC from normal immunosuppressive pathways has already entered the clinical arena SC. Until recently, exclusively the presence of the fused BCR-ABL with promising clinical results. A better knowledge of the immuno- gene by FISH in the purified LSC fraction, allowed researchers to logic phenotype of tumors and the role of check-points regulators, identify Ph+ LSC.1-4 Thus, up to date it has been quite difficult to such as PD-1 and CTLA-4, IDO enzyme function and MSCs in the identify and possibly quantify bone marrow residual CML LSCs induction of immunological tolerance against tumors, is important during TKI treatment due to their small number and to a low-sen- to understand critical pathways for the manipulation of anti-tumor sitive time-consuming technique based on cell separation. The pos- immune response. In particular, immune cell-rich tumors may opti- sibility to easily detect and monitor the behavior of CML LSC dur- mally respond to targeting of negative immune regulators (e.g. lym- ing TKI treatment, in term of rate and timing of reduction and ot phomas) while non T-cell infiltrated cancers may require the induc- correlate it with the molecular response would open a great oppor- tion of inflammation to optimize immune responses. This transla- tunity to explore further the role of TKI in this disease. tional research is instrumental, at the clinical level, for the devel- Several surface markers such as CD123, CD25, CD117, IL1RAP, opment of novel molecules and strategies to counteract these ST2, CD26 have been recently proposed to be upregulated on can- tolerogenic pathways .In this presentation, some of the most impor- didate CML stem cells, but few have so far been proven to separate tant immunosuppressive mechanisms will be briefly reviewed as Ph1 positive from negative LSCs. Recent studies have shown that well as their potential role as targets of novel antitumor strategies. within the CD34+/CD38– population, the expression of IL1RAP may identify CML LSCs although the presence of this marker has been showing also in acute myeloid leukemia and normal References hematopoietic SCs.5 Landberg et al. have studied the expression of IL1RAP and CD25 on bone marrow isolated 1. Munn DH, Bronte V. Immune suppressive mechanisms in the tumor microen- CD34+/CD38–CML cells. These authors proposed that IL1RAP vironment. Cur Opinion in Immunology 2016; 39: 1-6. expression, as a measure of LSC burden at diagnosis of CML pre- 2. Zeng Z, Shi YX, Samudio IJ et al. Targeting the leukemia microenvironment dicts therapy outcome.6 Other studies showed that CD25 antigen by CXCR4 inhibition overcomes resistance to kinase inhibitors and is expressed in human CML Leukemia Initiating Cells (LICs) and chemotherapy in AML. Blood 2009; 113: 6215–24. 7 3. Gajewski T, Schreiber H and Xin Fu Y. Innate and adaptive immune cells in its expression positively correlates with CML disease progression. the tumor microenvironment. Nat Immunol 2013; 14: 1014-22. Herrmann et al. described that CD34+/CD38–/Lin– CML LSC 4. Rossi L, Salvestrini V, Ferrari D et al. The sixth sense: Hematopoietic Stem specifically co-express dipeptidylpeptidase IV (DPPIV= CD26) and Cells detect danger through purinergic signalling. Blood 2012; 120: 2365-75. that this enzyme disrupts LSC-niche interactions by degrading 5. Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: 8 immunoselection and immunosubversion. Nat. Rev. Immunol. 2006; 6: 715- SDF-1. Based on these data, CD26 appears to be a potential bio- 27. marker for the quantification and isolation of CML LSC, both in 6. Dunn GP, Bruce AT, Ikeda H et al. Cancer immunoediting: from immunosur- bone marrow and in peripheral blood.9 As such Culen et al. recently veillance to tumor escape. Nat. Immunol. 2002; 3, 991-8. quantified CD26+ LSCs bone marrow compartment in 31 CML 7. Ustun C, Miller JS, Munn DH et al. Regulatory T cells in acute myelogenous leukemia: is it time for immunomodulation? Blood 2011; patients at diagnosis and their number appears to correlate with response to TKIs treatment.10 However, the feasibility to detect peripheral blood (PB) CML LSCs by flow-cytometry has never explored thoroughly. Recently, we focused our research on testing and optimizing a new system to detect CML LSCs in PB by using a flow-cytometry multi-parameters approach. Firstly, the specificity of the CD34+/CD38–/CD26+ antibody panel to identify CML LSCs has been validated by FISH analysis of PB sorted cells in CML patients. On the contrary, the flow-cytometry assessment of PB CD26+ LSCs always scored negative when performed in normal subjects, non- CML patients undergoing G-CSF treatment and subsequent CD34+ haematologica | 2016; 101(s3) | S1 Main Program cell mobilization, patients with Ph- myeloproliferative disorders, functional platelet defects. The degree of
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