| Abstract [eng] |
With application of modern treatment, most acute leukemia patients achieve complete clinical and morphological remission, however some of them eventually relapse due to the persistence of leukemic cells. We tried to verify the hypothesis that the detection of aberrant phenotypes by flow cytometry may show leukemic cells to be resistant to treatment and therefore residing in the patient's bone marrow, even when intensive chemotherapy is applied. The aim of the study was to identify aberrant phenotypes and parameters of multidrug resistance in acute leukemia patients and assess their impact on minimal residual disease dynamics. 114 patients with newly diagnosed acute leukemia were included in the study. 35 patients had acute B-lymphoblastic leukemia, 29 - acute T-lymphoblastic leukemia, 50 - acute myelogenous leukemia. The control group consisted of 12 healthy bone marrow donors. Aberrant leukemia associated phenotypes, multidrug resistance and minimal residual disease were studied by flow cytometry. Multidrug resistance has been studied determining the expression of multidrug resistance related proteins (P-gp, MRP1) on the surface of leukemic cells and examining their function by detecting an accumulation of calcein within the cell. The response to treatment was assessed applying the original flow cytometric assay for minimal residual disease detection. We found that several aberrant phenotypes of patients with acute myelogenous leukemia (CD13+CD33+CD56+, CD5+, CD7+) are related to an increased multidrug resistance and through this mechanism influence a higher level of minimal residual disease. Aberrant phenotypes of patients with acute lymphoblastic leukemia did not correlate with parameters of multidrug resistance, yet several phenotypes were associated with a higher or lower minimal residual disease. These phenotypes influence the number of residing during treatment leukemic cells by biological mechanisms other than multidrug resistance. In summary, the assessment of aberrant leukemia associated phenotypes and multidrug resistance by flow cytometry can provide important prognostic information and help to identify groups of patients who would benefit from individualized treatment. |
