Introduction: It is believed that the reason of the leukemic clone cell resistance to treatment with tyrosine kinase inhibitors during chronic myeloid leukemia (CML) is mutations in the genome of an early bone marrow progenitor cells that are CD34-positive. Such cells, regardless of treatment, acquire ability to proliferation and differentiation. This leads to the re-expansion of the CD34 + cells. Aim: to determine the CD34 antigen expression in bone marrow and peripheral blood cells in CML patients with different response to imatinib therapy using the results of hematopoietic cells culturing and the data of flow cytometry. Methods: Bone marrow aspirate from 39 patients who were treated with imatinib was studied with cytogenetic, flow cytometry and culture methods in vitro. Results: In patients with an optimal response to imatinib therapy the number of colonies was 1.8 times lower than the number of those in the group of patients with a suboptimal response to therapy. In turn, in patients with failure of imatinib therapy the number of colonies was the highest and was 2.1 times higher than the patients with optimal response. The results of cytometric studies have shown that the number of CD34 + cells in bone marrow was significantly higher compared to the number of CD34 + cells in peripheral blood cells and increased with the acquisition of leukemic cells the resistance to imatinib. There was a direct correlation between the number of colonies and clusters in semisolid agar in vitro and the number of CD34 + cells in the bone marrow of patients. Conclusions: The correlation between the number of CD34 + cells and the number of cell aggregates in semisolid agar in vitro indicates the prognostic value of the method for determining CD34 + cells in the patient bone marrow.The parallel increase of their number in the peripheral blood will allow developing express methods for the detection of individual patient response to imatinib therapy.
The paper presents an effective method of the monitoring of individual response of the patients with chronic myeloid leukemia (CML) to the therapy with tyrosine kinase inhibitors (TKi). The growth patterns analysis of hematopoietic cells from CML patients showed that functional activity of bone marrow progenitor cells of the patients with complete response to TKi therapy was significantly lower (p < 0.05) in comparison with the colony-forming efficiency of bone marrow sampled from patients with a resistance to the therapy. The correlations were revealed between numbers of colony-forming units and the percentage of Ph+ cells in the bone marrow. This correlation was positive for the group of patients who were alternatively treated with the hydroxyurea and negative for the group of individuals with the resistance to TKi therapy.
Summary. Aim: To assess the expression of Ki-67 protein and CD34 antigen on peripheral blood (PB) and bone marrow (BM) cells in chronic myelogenous leukemia (CML) patients with different response to tyrosine kinase inhibitors (TKI) imatinib (IM) and nilotinib (NI) therapy. Patients and Methods: BM aspirate and PB samples from 41 CML patients treated with IM and NI were studied by cytogenetic, molecular genetic, and flow cytometry methods. According to the response to TKIs, the patients were distributed into the optimal response, warning, and treatment failure groups. Results: The patients with optimal response to TKI therapy showed the lowest levels of Ki-67 expression in PB and BM compared with the patients from warning and falure treatment groups, however, Ki-67 expression was close to the reference values in PB (0.7 ± 0.3)%, only in NI-treated patients, The highest expression of Ki-67 in PB was observed in patients from treatment failure groups. In PB of patients who received NI and did not achieve optimal response, CD34+ cell count increased by almost 4 times compared with that in the optimal response group. The results indicated that CD34+ cell pool expanded in patients with poor response to both IM and NI. In patients with optimal response to NI therapy, CD34+ cell counts in PB were within the reference range and did not exceed 0.5%. Similar results were observed for Ki-67 and CD34+ in BM hematopoietic cells. Conclusions: Ki-67 expression and CD34+ cell count in PB and BM of CML patients increased with the acquisition of clonal resistance to IM and NI. NI provides a deeper molecular response compared with IM.
Background:The main feature of CML is the formation of the BCR-ABL gene, the product of which has a pronounced tyrosine kinase activity, which is due to the suppressing effect of the protein regulators of proliferation and apoptosis. The result is an increase of the proliferation of tumor cells, the marker of which is the Ki-67 protein. It is also known that the cause of the leukemic clone cell resistance to TKI treatment is the mutations in the genome of the early CD34+-progenitor cells that acquire the ability to proliferate. This leads to the expansion of CD34+cells Aims: Evaluate the expression of Ki-67 protein and antigen CD34 by haematopoietic cells of PB and BM in CML patients with different response to imatinib (IM) and nilotinib (NI) therapy. Methods: We included 67 patients with CP-CML treated with IM and 22 patients treated with NI in study. The studies were conducted on a FACscan flow laser cytometer. The number of cells expressing Ki-67 and CD34-cells was determined. Results: Data analysis showed that in CML patients with the best response to TKI therapy the lowest values of Ki-67 protein expression were observed in PB and BM in comparison to patients of all other groups, but only in patients treated with NI this indicator was close to the reference values in PB (0.7 ± 0.3)%, whereas in patients taking IM it was equal to (2.86 ± 1.3)%, on the basis of which it can be assumed that NI is more potently acts on the stem leukemic cells. A comparison between groups with different responses to TKI treatment showed that the highest expression of Ki-67 in PB was observed in patients with unsatisfactory response. Thus, the Ki-67 score was 7 times higher in the warning group and more than 6 times higher in the treatment failure group compared with the optimal response (p < 0.05) in both groups with IM and NI. The difference in expression of KI-67 in patient groups who received IM and NI and did not achieve a good response is not indicated. Similar results were obtained in the study of BM. Immunophenotypic quantitative monitoring of CD34+-cells in PB and BM in CML patients with a different response to IM and NI therapy was performed. Data analysis showed that in the PB of patients with an unsatisfactory response, the number of CD34+-hemopoietic precursor cells exceeded the same value in patients with the optimal response (p < 0.05). Thus, the expression of CD34 in warning group patients to IM therapy was 2.4 times higher than the optimal response, and in the group of failure therapy -4.3 times. Concerning the expression of CD34 in the PB of patients treated with NI and did not achieve optimal response, there was an increase of CD34+ cells in the PB by almost 4 times compared with the optimal response group. The results suggest that the pool of CD34+ cells is expanded in the PB of patients with an unsatisfactory response to both IM and NI. It should be noted that in patients with an optimal response to NI, expression of CD34+ cells in the PB was within the reference range and did not exceed 0.5%. Instead, in pati...
Patients with MDS RAEB II were examined. The decrease in dynamics of intracellular K³-67 protein expression was determined in patients with MDS RAEB II with positive response to chemotherapy, and the increase in proliferative activity of haematopoietic cells of peripheral blood (PB) and bone marrow (BM) was determined in patients with MDS RAEB II in transformation and acute myeloid leukaemia (AML) after MDS.
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