Svyezhentseva I. Morphologicalfunctional characteristics of chronic myeloid leukemia erythroid and granulocyte-macrophage hematopoietic cells of pathients treated with tyrosine kinase inhibitors in cell cultures in vitro and in vivo

Identification of the effectiveness of targeted therapy drugs criteria for leukemic clone cells in chronic myeloid leukemia (CML) is a current issue of modern hematology, cell biology and medicine. It was established that cells of leukemic clone are capable of differentiating into all parts of hematopoietic cells, including erythroid lineage. There is no reliable data on the role of erythropoiesis in the formation of resistance to tyrosine kinase inhibitor therapy (TKI). In this research we have studied the ability of erythroid and granulocyte-macrophage progenitor cells to form cell aggregates in semisolid medium. To set the sensitivity of leukemic cells clone to soluble factors of normal microenvironment we have cultivated erythropoietic and granulocytopoietic progenitor cells in diffusion chambers in vivo. Correlative relationship was found between the number of erythroid colonies and the number of leukemic cells in the patient's bone marrow. It was established that the acquisition of resistance by leukemic clone cells to TKI is characterized by increased proliferative activity and insensitivity to the presence or absence of soluble microenvironmental factors, granulocyte-macrophage colony stimulating factor and erythropoietin in the culture medium. It was revealed that previous chemotherapeutic therapies adversely affected the subsequent response of leukemic clone cells to TKI. It is probably due to the accumulation of additional genetic abnormalities that contribute to resistance to drugs. It was proved that prognostic value of patient's bone marrow cells functional activity is comparable with a recognized prognostic factor - Sokal index.