PF402 PECULIARITIES OF THE EXPRESSION OF KI‐67 AND CD34 HEMOPOIETIC PRECURSOR CELLS IN PB AND BM OF CML PATIENTS WITH THE DIFFERENT RESPONSES TO IMATINIB AND NILOTINIB THERAPY
Authors: Perekhrestenko T. , Sviezhentseva I. , Melnyk U. , Dyagil I. 
Published: June 2019

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+cellsAims: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 patients who received IM and achieved the optimal response, the cell content did not decrease below 4%. In the study of CD34+‐cell expression in the BM, the difference was also found between the groups of optimal response and the ineffectiveness of therapySummary/Conclusion:Thus, the number of Ki‐67 and CD34+‐cells in PB, BM of CML patients increases with the acquisition of leukemic clone cells resistance to IM and NI. NI can provide a more profound molecular response because of its ability to more actively influence stem leukemia cells.