Research Groups

Dimitar Efremov

Molecular Hematology

Group Leader
Research Interests and Description
Group Members
Montertondo Outstation

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

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. doi: 10.1016/j.cellsig.2009.03.007

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

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

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

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

Laurenti, L., Tarnani, M., De Padua, L., Efremov, D.G., Zini, G., Garzia, M., Piccirillo, N., Chiusolo, P., Sorà, F., Innocenti, I., Sica, S., Leone, G. 2008. 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.  87, 891-898

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

Efremov, D.G., Gobessi, S., Longo, P.G. 2007 Signaling pathways activated by antigen-receptor engagement in chronic lymphocytic leukemia B-cells. Autoimmun Rev. 7, 102-108

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. 2007. CD38 and ZAP-70 are functionally linked and mark CLL cells with high migratory potential. Blood 110, 4012-4021

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

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

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

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

Panovska-Stavridis, I., Ivanovski, M., Siljanovski, N., Cevreska, L., Efremov, D.G. 2007. 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. 31, 245-248

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; 31:253-6.

Yan, X.J., Albesiano, E., Zanesi, N., Yancopoulos, S., Sawyer, A., Romano, E., Petlickovski, A., Efremov, D.G., Croce, C.M., Chiorazzi, N. 2006. B cell receptors in TCL1 transgenic mice resemble those of aggressive, treatment-resistant human chronic lymphocytic leukemia. Proc Natl Acad Sci USA 103, 11713-11718

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

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

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

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

Messmer, B.T., Albesiano, E., Efremov, D.G., Ghiotto, F., Allen, S.L., Kolitz, J., Foa, R., Damle, R.N., Fais, F., Messmer, D., Rai, K.R., Ferrarini, M., Chiorazzi, N. 2004. Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia. J. Exp. Med. 200, 519-525

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

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

Pavkovic, M., Georgievski, B., Cevreska, L., Spiroski, M., Efremov, D.G. 2003. CTLA-4 exon 1 polymorphism in patients with autoimmune blood disorders. Am. J. Hematol. 72, 147-914

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