Print Friendly Version of this pagePrint Get a PDF version of this webpagePDF

 

 

FACULTY OF MEDICINE

 

Current treatments are able to cure more than 70% of children with malignant diseases. However, only 50% of patients can be cured from acute myeloid leukemia. The failure to treat this disease is caused mainly by recurrences and complications resulting from intensive multi-drug chemotherapy. Scientists from Jagiellonian University are trying to increase children's chances of being completely cured of this disease.

Why is cancer so challenging for science? The answer is that while healthy cells divide, differentiate, and die in a controlled way, cancer cells are not subject to such regulatory mechanisms. It is very difficult to control the expansion of cancer cells in the body. This is why it is so important to learn more about the processes that occur in cancer cells in order to develop more effective treatment methods.

Broadening our knowledge about the illness

The team from the Department of Pediatric Oncology and Hematology (Jagiellonian University Medical College) is working on acute myeloid leukemia (AML), a malignant disorder of the hematopoietic system which accounts for approximately 20% of all cases of leukemia in children, leads to anemia and decreased immunity, and can be fatal if untreated.

The team is conducting multidirectional research on specific types of AML with the goal of detecting specific cancer markers. This research may also contribute to the development of more optimized therapies adapted to relevant groups of patients. The main objective of these studies is to obtain comprehensive knowledge about the biology of acute leukemia in children.

In most patients with AML, various types of chromosomal or genetic disorders are found in leukemic cells. They are responsible for the production of pathological proteins which cause disorders of the hematopoietic system. Characteristic chromosomal disorders and specific genetic mutations are used as diagnostic and prognostic markers and indicators of treatment efficacy.

Minimum residual disease

The term minimum residual disease (MRD) is used to describe a small amount of leukemic cells that do not cause clinical symptoms and are impossible to detect using morphologic assessment with a light microscope. The determination of MRD levels enables doctors to detect patients who have a higher risk of recurrence in spite of successful remission. Currently, immunological and molecular methods use markers that are characteristic of leukemic cells to determine MRD. The detection of surviving malignant cells during treatment is essential for prognosis and constitutes a basis for the modification of therapy. Monitoring MRD after the end of treatment is key to predicting a potential recurrence of AML.

Communication between cells

Each cell has the ability to receive, select, analyze, and respond to signals transmitted from the environment and from other cells through receptors located on its surface. Intercellular signaling is a process that is necessary for proper bodily function, as it determines the regulation of the metabolism, survival, proliferation (multiplication), differentiation, and death of cells. Tyrosine kinases, among others, play a key role in this process. Tyrosine kinases are one of the basic types of proteins in the human body that influence the biological activity of other proteins. Scientists from the Department of Pediatric Oncology and Hematology are focusing mainly on the tyrosine kinase of the c-KIT receptor, which plays a multi-dimensional role both in the regulation of growth and differentiation of cells in hematopoietic and in the functioning of bone marrow and blood cells. The c-KIT receptor is a specific spot on the surface of cells which is influenced by relevant factors in areas such as growth. This process can be compared to a lock (receptor) and key (growth factor). Unfortunately, this receptor is activated in an inappropriate way in acute myeloid leukemia, resulting in the excessive, uncontrolled proliferation of leukemic cells and the inhibition of the so-called programmed death of cells (apoptosis), which is a process that is essential to proper bodily function.

Treatment strategies and test results

Targeted therapies are a new method for treating malignant diseases. These therapies involve the application of substances (inhibitors) that specifically block the pathological protein which production causes the abnormal behavior of cells. As a result of the employment of such a therapeutic strategy, the application of a given molecule is limited only to situations where a protein specifically influencing the molecule is present in the cells of the treated cancer.

Due to the fact that the neoplastic process in AML may be connected with the transmission of a signal originating from the c-KIT receptor, it is theoretically possible to inhibit this process by applying substances that block the enzymatic activity of the kinase of this receptor.

The research results enabled us to focus on several important disorders occurring in leukemic cells in AML and to distinguish more important prognostic factors (related to the prognosis of illness development). The inclusion of tyrosine kinase inhibitors of the c-KIT receptor in the study enabled us to completely block the growth of cells of acute myeloid leukemia in vitro and to direct them towards apoptosis. The research also allowed us to analyze markers that are useful in the search for residual disease.

The aim of these studies is to improve the diagnostic standards in AML, which would enable us to more accurately determine types of leukemia and to put suffering children in the appropriate therapeutic groups in order to start personalized treatment. The detection of active mutations may contribute to the development of new pharmacological strategies. Apart from the cognitive nature of the studies carried out by the team, the results are likely to contribute to the development of personalized medicine. "We are planning to develop new therapeutic methods, adapted to the molecular disorders in malignant cells, in the future. This will improve the efficacy of cancer treatment and reduce the risk of complications," says Professor Walentyna Balwierz, the head of the research team.


Research team:
Polish-American Institute of Pediatrics, Jagiellonian University Medical College, and Children's University Hospital of Kraków Department of Pediatric Oncology and Hematology: Professor Walentyna Balwierz, MD, PhD; Angelina Moryl-Bujakowska, MD, PhD; Tomasz Klekawka, MD, PhD; Katarzyna Pawińska-Wąsikowska, MD, PhD; Małgorzata Czogała, MD, PhD; Małgorzata Szurgot, MD; Małgorzata Lasota
Chair of Pediatrics, Department of Pediatrics, and Department of Medical Genetics: Professor Jacek J. Pietrzyk, MD, PhD; Professor Mirosław Bik-Multanowski, MD, PhD; Teofila Książek; Katarzyna Szewczyk