Myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), and acute leukemias (ALs) are clonal hematological disorders resulting from multiple genetic alterations in hematological stem cells. MDS is characterized by profound cytopenias due to ineffective hematopoiesis and resulting in significant compromise in quality and quantity of life. Life expectancy in a newly diagnosed MDS patient varies from some months to ten years. MPNs are group of related hematological disorders characterized by excess formation of mature blood cells. Both MPN and MDS have a tendency to transform into acute myeloid leukemia (AML), which significantly worsens the prognosis of the disease. Most commonly, these diseases are diagnosed in patients over 50 years of age and familial predisposition should be suspected in patients acquiring the disease in the early adulthood or in childhood.

ALs, in turn, consist of a group of hematopoietic neoplasms involving patients of all ages. Cancer cells, namely blasts, reside in the patient’s bone marrow and are characterized with an impaired capacity to develop to mature myeloid or lymphoid blood cells. Depending on the age and performance status of the patient and subtype of the disease, acute leukemias lead to death in 10-80% of cases despite the given anti-cancer therapy. Acknowledging pathological events occurring in hematopoiesis also uncovers the path to understanding normal physiological processes in the blood cell development.

Already today, detection of germline mutations also affects the mode of therapy e.g. timing of stem cell transplantation, and selection of the donor. Knowledge on the prevalence of mutations, their penetrance and effects on the clinical phenotype is also a prerequisite for successful genetic counseling. In addition to dominant high-penetrance mutations, relatively common genetic variation may contribute to tumorigenesis.

The aim of our research is to understand how inherited and acquired genetic factors contribute to the development and clinical course of hematological malignancies.