About the project and description of the research programme

Status of the Scientific Investigations in the Respective Research Field in Bulgaria

Hematological malignancies in Bulgaria account for 1410 new cases annually while the prevalence is estimated to be 168,4 patients/100000 persons. Because of the poor prognosis in most of the cases and the significant cost of disease management these entities confer a considerable burden to health care system (Danon S. 2007). On the other hand the outstanding recent advances in the understanding of biology of these disorders opens wide avenues for rapid translation of basic research findings into clinically relevant practice.

Hematology-related research in Bulgaria had its landmark discovery with the identification of the first chromosomal translocation associated with Burkitt’s lymphoma (Manolov and Manolova 1972, Manolova, et al 1979, Mitelman, et al 1979). Subsequently, following the relevant technological researchers and teams from the organization participating in this project proposal performed extensive studies on the ultrastructural and morphological characteristics of malignant cells (Dobreva and Meshkov 1977, Dobreva and Meshkov 1979, Krahnert, et al 1986, Michailov, et al 1990, Seeber, et al 1979), cytogenetic features of different entities (Balatzenko, et al 2003, Mitev, et al 1996a, Mitev, et al 1998a, Mitev, et al 1996b, Mitev, et al 1998b, Nacheva, et al 1982), the expression of specific surface markers on the malignant cell populations (Guenova 2000, Michova 2003, Nikolova, et al 1998, Taskov, et al 1995), extensive molecular studies on the expression of clinically and biologically relevant genes (Balatzenko and Guenova 2000), clinical experience reports on the management of some hematological malignancies (Avramova, et al 2006, Goranova- Marinova, et al 2007, Konstantinov, et al 1998a, Nenova, et al 2005, Yaneva, et al 2006), several epidemiological studies (Parkin, et al 1992, Shivarov, et al 2005). More recently several studies from our group aimed at the predictive power of the expression of several drug resistance genes, key apoptosis-related proteins in the pathogenesis of leukemias (Guenova, et al 2008), as well as at the approaches for the detection of minimal residual disease (Balatzenko, et al 2002). Besides, a number of level D evidences were published in the form of clinical reports either for the peculiar cellular origin or biologic and clinical behaviour of cases with malignant blood disorders (Balatzenko, et al 2003, Balatzenko, et al 2008, Balatzenko, et al 2004, Boneva, et al 1996, Grudeva-Popova, et al 2007, Guenova, et al 1997, Mihailov, et al 2007, Shivarov, et al 2006, Shivarov 2008, Staneva, et al 2004). Recent basic Hematology-oriented research included studies on the cytotoxic activity of various agents on leukemic cells (Alaikov, et al 2007, Bakalova, et al 2008, Berger, et al 2003, Georgieva, et al 2002, Konstantinov, et al 1998b, Konstantinov, et al 1999, Konstantinov, et al 2002, Konstantinov, et al 1998c, Kostova, et al 2005, Kostova, et al 2001, Manolov, et al 2000, Momekov, et al 2006a, Momekov, et al 2006b, Nikolova, et al 2004, Vasilev, et al 2005, Yosifov, et al 2007) and on signaling pathways involved in oncogenesis (Hristov, et al 2005, Hristov, et al 2007, Iankov, et al 2002). Finally, the group from the Medical University in Varna focused on the role of microenvironment and studied the role of angiogenesis and its clinical significance in chronic myeloproliferative disorders and some other haematological malignancies (Zhelyazkova, et al 2008).

An established CoE for Translational Research in Hematology will strengthen the network activities between the leading Clinical Hematology centers located in some of the biggest cities in Bulgaria.

The unbiased analysis of the research activity in Bulgaria in the field of Neoplastic Hematology reveals that the efforts have always been focused on the catching up with the high standards in the European countries and have achieved even leading positions in Oncology and Oncological Hematology with regard to the rapid transfer of research data and high technology approaches into clinical practice aiming at harmonization of diagnostics and standardization of integrated clinical, morphological, immunological and molecular studies. Obviously, those activities have been concentrated in several institutions: National Center of Hematology and Transfusiology (currently National Specialized Hospital for Active Treatment of Haematologic Diseases (NSBALHZ) – Sofia; Medical University – Sofia; Military Medical Academy – Sofia; Medical University – Plovdiv; Medical University – Varna; and Medical University – Varna.

It is of note, however, that most of the studies suffered from the lack of integrated multidisciplinary approach. The exceptions appeared to be the studies performed at the National Center of Hematology and Transfusiology (currently National Specialized Hospital for Active Treatment of Haematologic Diseases (NSBALHZ) – Sofia, where the studies were based on the intergration of gentic, molecular, morphological and immunological studies under specified clinical settings. The advantage of the National Specialized Hospital for Active Treatment of Haematologic Diseases (NSBALHZ) is probably due to long-term functioning of several laboratories – the Laboratory of Cytopathology, Histopathology, Immunology and Immunochemistry and the Laboratory of Cytogenetics and Molecular Biology and the strong collaboration with the local clinical department. A national-wide recognized multidisciplinary team has been developed on those grounds that has steadily been demonstrating its potential for conducting retrospective and prospective studies in Oncological Hematology in its individual capacity and also in good collaboration with other research and clinical groups. A working integrated laboratory and clinical infrastructure and a favourable environment has been established and proved its advances for many years at national level that attracts not only collaborators, but also patients from all over the country representing the entire spectrum of hematological malignancies and the rare subtypes in particular, which is also a major prerequisite for stable translational research programs. Thus, it is a logical and justified step in the development of the institution to become a host of a Center of Excellence for Translational Research in Hematology (CETRH) which establishment will be based predominantly on the preexisting laboratories mentioned above. Furthermore, such a CETRH does not aims only at the development of a single institution but rather to enhance the collaboration between the leading Hematological units in the country and to promote the performance of local and nation-wide research activities driven by the “bench to bedside” approach.