Research Groups

Molecular Hematology

Group Leader

Research Interests and Description
Group Members
Montertondo Outstation

Dimitar Efremov

Molecular Hematology Laboratory
Monterotondo Outstation
International Centre for Genetic Engineering and Biotechnology
CNR Campus "Adriano Buzzati-Traverso"
Via E. Ramarini 32
I-00016 Monterotondo Scalo (Rome)
ITALY

E-mail: efremov@icgeb.org
Tel: +39-06-90091300
Fax: +39-06-90091260

Education

Faculty of Medicine, University of St. Cyril and Methodius, Skopje, Macedonia, MD, 1986
State exam and license for Medical practice, 1989
University of Limburg, Maastricht, The Netherlands, PhD., 1994
Faculty of Medicine, Univ. St. Cyril and Methodius, Skopje, Macedonia, Specialist in Internal Medicine-Hematology, 1999

Career History

Since 2004, Staff Scientist and Head of the ICGEB Molecular Hematology Group at the Monterotondo Outstation, Rome, Italy.
Since 2001, Associate Professor of Internal Medicine, Department of Hematology, Faculty of Medicine, Skopje, Macedonia.
1998-2001, Assistant Professor, Department of Hematology, Faculty of Medicine, Skopje, Macedonia.
1994-1997, Assistant Research Scientist, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
1993, Visiting Scientist, Medical College of Georgia, Augusta, Ga, USA.
1992, Post-doctoral fellow, ICGEB, Trieste, Italy.
1990-1992, Resident, Department of Hematology, Faculty of Medicine, Skopje, Macedonia.
1988-1989, Research Associate, Research Center for New Technologies, Macedonian Academy of Sciences and Arts, Skopje.
1987, Visiting Scientist, Medical College of Georgia, Augusta, Ga, USA.

Teaching Activity

Since 2004, external lecturer at the School for Specialization in Hematology, Catholic University Hospital "A. Gemelli", Rome.
Since 2001, Associate Professor of Internal Medicine, Faculty of Medicine, Skopje, Macedonia.
1998-2002, lecturer at the Interdisciplinary Postgraduate Studies in Molecular Biology and Genetic Engineering, University "St. Cyril and Methodius", Skopje.
1998-2001, Assistant Professor of Internal Medicine, Faculty of Medicine, Skopje.

Scientific Activity

His research interests encompass many aspects of hematological and immunological disorders, especially hematological malignancies, autoimmune cytopenias and the thalassemias. Most of the current research is related to the investigation of the cellular and molecular mechanisms governing the development and progression of B-cell neoplasms, in particular chronic lymphocytic leukemia and B-cell lymphomas. Novel biologic prognostic markers and therapeutic strategies are also an area of major interest.

Other Activities

Member of several international associations and expert groups, including the American Society of Hematology, the American Society of Clinical Oncology, the European Group for Blood and Marrow Transplantation, the UNESCO expert committee for scientific cooperation in Southeast Europe, the National Committee for Registration of Medicines and the MASA committee on the National strategy for the development of the health sector in the Republic of Macedonia, and the Editorial Board of the Balkan Journal of Medical Genetics. Served also as consultant physician for the European Commission office in Macedonia.

Selected publications

Bilous N, Bomben R, Dal Bo M, Capello D, Forconi F, Laurenti L, Bertoni F, Efremov DG, Marasca R, Del Poeta G, Martina Z, Kryachouk I, Dyagil I, Gaidano G, Chumak A, Gattei V, Abramenko I. Molecular and clinical features of chronic lymphocytic leukemia with stereotyped B-cell receptors in a Ukrainian cohort. Leuk Lymphoma. 2010; 51:822-838

Bomben R, Dal-Bo M, Benedetti D, Capello D, Forconi F, Marconi D, Bertoni F, Maffei R, Laurenti L, Rossi D, Del Principe MI, Luciano F, Sozzi E, Cattarossi I, Zucchetto A, Rossi FM, Bulian P, Zucca E, Nicoloso MS, Degan M, Marasca R, Efremov DG, Del Poeta G, Gaidano G, Gattei V. Expression of mutated IGHV3-23 genes in chronic lymphocytic leukemia identifies a disease subset with peculiar clinical and biological features. Clin Cancer Res. 2010; 16:620-628

Bulian P, Tarnani M, Rossi D, Forconi F, Del Poeta G, Bertoni F, Zucca E, Montillo M, Pozzato G, Deaglio S, D'Arena G, Efremov D, Marasca R, Lauria F, Gattei V, Gaidano G, Laurenti L. Multicentre validation of a prognostic index for overall survival in chronic lymphocytic leukaemia. Hematol Oncol. 2010; DOI: 10.1002/hon.959

Efremov, D.G. 2010. Chic adaptor regulates apoptosis in CLL. Blood 115, 3647-3648 PubMed link

 

Bomben R, Dal Bo M, Capello D, Forconi F, Bertoni F, Maffei R, Laurenti L, Rossi D, Zucca E, Degan M, Marasca R, Efremov DG, Del Poeta G, Gaidano G, Gattei V. IGHD3-3 fails to behave as unfavourable prognostic marker in chronic lymphocytic leukaemia. Br J Haematol. 2010; 149:299-302

Dal-Bo M, Bertoni F, Forconi F, Zucchetto A, Bomben R, Marasca R, Deaglio S, Laurenti L, Efremov DG, Gaidano G, Del Poeta G, Gattei V. Intrinsic and extrinsic factors influencing the clinical course of B-cell chronic lymphocytic leukemia: prognostic markers with pathogenetic relevance. J Transl Med. 2009; 7:76

Carsetti, L., Laurenti, L., Gobessi, S., Longo, P.G., Leone, G., Efremov, D.G. 2009. Phosphorylation of the activation loop tyrosines is required for sustained Syk signaling and growth factor-independent B-cell proliferation. Cell Signal 21, 1187-1194 PubMed link

Tolusso B, De Santis M, Bosello S, Gremese E, Gobessi S, Cuoghi I, Totaro MC, Bigotti G, Rumi C, Efremov DG, Ferraccioli G. Synovial B cells of rheumatoid arthritis express ZAP-70 which increases the survival and correlates with the inflammatory and autoimmune phenotype. Clin Immunol. 2009; 131:98-108

Bomben R, Dal Bo M, Capello D, Forconi F, Maffei R, Laurenti L, Rossi D, Del Principe MI, Zucchetto A, Bertoni F, Rossi FM, Bulian P, Cattarossi I, Ilariucci F, Sozzi E, Spina V, Zucca E, Degan M, Lauria F, Del Poeta G, Efremov DG, Marasca R, Gaidano G, Gattei V. Molecular and clinical features of chronic lymphocytic leukaemia with stereotyped B cell receptors: results from an Italian multicentre study. Br J Haematol. 2009; 144:492-506

Gobessi, S., Laurenti, L., Longo, P.G., Carsetti, L., Berno, V., Sica, S., Leone, G., Efremov, D.G. 2009. Inhibition of constitutive and BCR-induced Syk activation downregulates Mcl-1 and induces apoptosis in chronic lymphocytic leukemia B-cells. Leukemia 23, 686-697 PubMed link

Laurenti L, Tarnani M, De Padua L, Efremov DG, Zini G, Garzia M, Piccirillo N, Chiusolo P, Sorà F, Innocenti I, Sica S, Leone G. Oral fludarabine and cyclophosphamide as front-line chemotherapy in patients with chronic lymphocytic leukemia. The impact of biological parameters in the response duration. Ann Hematol 2008; 87:891-898

Laurenti L, Tarnani M, Innocenti I, Savino G, Battendieri R, Larocca LM, Chiusolo P, Sorà F, Sica S, Efremov D, Leone G. Chronic Lymphocytic Leukemia With Eyelid Involvement Responding to Alemtuzumab. J Clin Oncol. 2008; 26:5299-5301

Longo, P., Laurenti, L., Gobessi, S., Sica, S., Leone, G., Efremov, D.G. 2008. The Akt/Mcl-1 pathway plays a prominent role in mediating antiapoptotic signals downstream of the B-cell receptor in chronic lymphocytic leukemia B cells. Blood 111, 846-855 PubMed link

Deaglio S, Vaisitti T, Aydin S, Bergui L, D'Arena G, Bonello L, Omede P, Scatolini M, Jaksic O, Chiorino G, Efremov D, Malavasi F. CD38 and ZAP-70 are functionally linked and mark CLL cells with high migratory potential. Blood. 2007; 110:4012-4021

Efremov DG, Gobessi S, Longo PG. Signaling pathways activated by antigen-receptor engagement in chronic lymphocytic leukemia B-cells. Autoimmun Rev. 2007; 7:102-8

Laurenti L, Tarnani M, Efremov DG,  Chiusolo P, Lai M, De Padua L,  Sica S, Leone G. Efficacy and safety of low-dose alemtuzumab as treatment of autoimmune hemolytic anemia in pretreated B-cell chronic lymphocytic leukemia. Leukemia. 2007; 21:1819-1821

Bomben R, Dal-Bo M, Capello D, Benedetti D, Marconi D, Zucchetto A, Forconi F, Maffei R, Ghia EM, Laurenti L, Bulian P, Del Principe MI, Palermo G, Thorsélius M, Degan M, Campanini R, Guarini A, Del Poeta G, Rosenquist R, Efremov DG, Marasca R, Foà R, Gaidano G, Gattei V. Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study. Blood. 2007; 109, 2989-2998

Gobessi S, Laurenti L, Longo PG, Sica S, Leone G, Efremov DG. ZAP-70 enhances B-cell receptor signaling despite absent or inefficient tyrosine kinase activation in chronic lymphocytic leukemia and lymphoma B-cells. Blood. 2007; 109:2032-2039

Laurenti L, Piccioni P, Tarnani M, De Padua L, Garzia M, Efremov DG, Piccirillo N, Chiusolo P, Sica S, Leone G. Low-dose thalidomide in combination with oral fludarabine and cyclophosphamide is ineffective in heavily pre-treated patients with chronic lymphocytic leukemia. Leuk Res. 2007; 31:253-256

Longo P, Laurenti L, Gobessi S, Petlickovski A, Pelosi M, Chiusolo P, Sica S, Leone G, Efremov DG. The Akt signaling pathway determines the different proliferative capacity of chronic lymphocytic leukemia B-cells from patients with progressive and stable disease. Leukemia. 2007, 21:110-120

Panovska-Stavridis I, Ivanovski M, Siljanovski N, Cevreska L, Efremov DG. Chronic lymphocytic leukemia patients with a V1-69 gene rearrangement do not have inferior survival with respect to patients that express other unmutated V(H) genes. Leuk Res. 2007, 31:245-248

Capello D, Zucchetto A, Degan M, Bomben R, Dal Bo M, Efremov DG, Laurenti L, Del Poeta G, Gaidano G, Gattei V. Immunophenotypic characterization of IgVH3-72 B-cell chronic lymphocytic leukaemia (B-CLL). Leuk Res. 2006; 30:1197-1199

Yan XJ, Albesiano E, Zanesi N, Yancopoulos S, Sawyer A, Romano E, Petlickovski A, Efremov DG, Croce CM, Chiorazzi N. B cell receptors in TCL1 transgenic mice resemble those of aggressive, treatment-resistant human chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2006; 103:11713-11718

Laurenti L, Petlickovski A, Rumi C, Gobessi S, Piccioni P, Tarnani M, Puggioni P, Marrietti S, Sica S, Leone G, Efremov DG. Comparison of ZAP-70/Syk mRNA levels with immunoglobulin heavy-chain gene mutation status and disease progression in chronic lymphocytic leukemia. Haematologica. 2005; 90:1533-1540

Laurenti L, Piccioni P, Tarnani M, Efremov DG, Fiorini A, Garzia M, Sica S. Low-dose intravenous alemtuzumab therapy in pretreated patients affected by chronic lymphocytic leukemia. A single center experience. Haematologica 2005; 90:1143-1145

Petlickovski A, Laurenti L, Li X, Marietti S, Chiusolo P, Sica S, Leone G, Efremov DG.  Sustained signaling through the B-cell receptor induces Mcl-1 and promotes survival of chronic lymphocytic leukemia B-cells. Blood, 2005; 105:4820-4827

Laurenti L, Piccioni P, Cattani P, Cingolani A, Efremov D, Chiusolo P, Tarnani M, Fadda G, Sica S, Leone G. Cytomegalovirus reactivation during alemtuzumab therapy for chronic lymphocytic leukemia: incidence and treatment with oral ganciclovir. Haematologica. 2004; 89, 1248-1252

Messmer BT, Albesiano E, Efremov DG, Ghiotto F, Allen SL, Kolitz J, Foa R, Damle RN, Fais F, Messmer D, Rai KR, Ferrarini M, Chiorazzi N. Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia. J. Exp. Med., 2004; 200, 519-525

Efremov DG, Georgievski B, Cevreska L, Pivkova A, Panovska I. Lamivudine treatment for acute hepatitis B virus infection during allogeneic peripheral blood stem cell transplantation. Bone Marrow Transplant., 2003; 31, 515-516

Pavkovic M, Georgievski B, Cevreska L, Spiroski M, Efremov DG. CTLA-4 exon 1 polymorphism in patients with autoimmune blood disorders. Am. J. Hematol., 2003; 72, 147-149