Domestic Projects

1. Ministry of Health of the Czech Republic, grant AZV 15-31540A “The Molecular Detection of Chronic Myeloid Leukemia by Patient-specific fusion of BCR-ABL1 gene: Impact on the effectiveness of therapy”

• The objective of the project is the molecular detection of chronic myeloid leukemia (CML) using the quantification of patient-specific fusions of BCR-ABL1 gene on the DNA level. We test the hypothesis that quantification on DNA level provides more accurate survey of CML course and TKI treatment in comparison with standard monitoring of BCR-ABL1 transcript levels.
• We expect a key benefit of BCR-ABL1 DNA quantification for patients in deep molecular responses with discontinuation of TKI therapy.

2. Ministry of Education, Youth and Sports of the Czech Republic, grant 32267/2015-1 “The Study of the epigenetic factors and tumor-suppressor genes regulating oncogene signaling pathways in models of leukemic hematopoiesis”

• The aim of the project is to support international scientific collaboration between the Institute of Hematology and Blood Transfusion, Prague, and the Marlene and Stuart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, USA, on the basic research study of epigenetic factors and tumor-suppressor genes regulating leukemogenic signal pathways.
• The project supports effective cooperation by sharing technologies established for analysis in one or the other institution.

3. Ministry of Health of the Czech Republic, Project for the Conceptual Development of the Institute of Hematology and Blood Transfusion

a) The study of regulatory links between miR-150, MYB and BCR-ABL1 in the CML pathogenesis (in collaboration with Prof. Tomas Stopka, First Medical Faculty, Charles University in Prague and Prof. Danilo Perrotti, University of Maryland, Baltimore, USA)

• We study whether miR-150 levels in leukemic hematopoietic stem and progenitor cells (HSPC) regulate MYB-dependent oncogenic pathways in CML.
• We hypothesize that such mechanism may affect resistance of leukemic HSPC to TKI and contribute (together with the defect in p53-mantained DNA control) to the transformation of CML chronic phase to blast crisis.

b) The study of resistance mechanisms to TKI (in collaboration with MD Ondrej Toman and MD Daniel Vyoral PhD; CLIP – Faculty Hospital Motol; Prof. Peter Valent, Vienna)

• We study mechanisms of acquired resistance to TKI at the models of BCR-ABL1 positive CML cell lines.
• The objective is to elucidate mechanisms of how BCR-ABL1 kinase domain´s mutations are acquired and to identify genetic and/or epigenetic predispositions for the development of this type of TKI resistance in CML patients.