EHA Library - The official digital education library of European Hematology Association (EHA)

It is believed that chronic myeloid leukemia arises as a result of myeloid progenitor cell malignancy. There are changing of proliferative activity in granulocyte-macrophage and erythroid hematopoiesis germs in patients bone marrow. Сurrently we don’t have definitive results regarding tyrosine kinase inhibitors influence on erythropoietic cell characteristics of patients with CML.

We studied 300 bone marrow samples from 75 patients: with initial diagnosis of CML (n = 7), patients receiving drug imatinib (n = 47) and patients who taking nilotinib (n = 21). We provide studying of erythroid mononuclears in semisolid in vitro and in vivo cultures. For in vivo culture we used special gel capsule, allowing cytokines and growth factors of mouse body affect human mononuclear cells. For in vitro culture we added 20% fetal calf serum, 30 ng/ml erythropoietin, and 20 ng/ml mlinterleykin-6 and interleukin-9. Cultivation was provided 14 days, then counted the number of erythroid colonies and provided their morphological studies.

The results showed that the increase of erythroid progenitor cells proliferation rates and the reduction of differentiation rates as a result of the parallel cultivation of patients’ bone marrow cells in vivo and in vitro happen irrespective of the presence of cytokines and growth factors in a normal microenvironment of these cultures. In addition, we showed that bone marrow cells of CML patients form erythroid colonies, when placed in the animals’ body without previous anemia. Moreover, correlative relationship was found between the number of erythroid colonies and the number of leukemic cells in the patients bone marrow. It was established that the acquisition of leukemic clone cells resistance to TKI is characterized by increased proliferative activity irrespective of soluble microenvironment factors as well as the culture medium in the erythropoietin presence.

The normal microenvironment factors not effect on the erythroid progenitor cell proliferation independence of the response to TKI therapy. This may explain the fact that we don’t have an increase the number of erythroid cells in patient bone marrow compared to culture in vitro. In addition, the ability of erythroid progenitor cells to form colonies in the absence of erythropoietin in culture can serve as an additional prognostic factor in the formation of resistance to TKI.