CHANGES IN STROMAL PROGENITOR CELLS DERIVED FROM BONE MARROW IN PATIENTS WITH CHRONIC MYELOGENOUS LEUKAEMIA AT THE ONSET OF THE DISEASE AND DURING TREATMENT

Abstract

Introduction. The properties of progenitor cells in the stromal microenvironment, i.e. multipotent mesenchymal stromal cells (MMSC) and fi broblast colony-forming units (CFU-F), undergo changes in patients with chronic myelogenous leukaemia (CML).Aim. To compare the progenitor cells of the stromal microenvironment (MMSCs and CFU-Fs) obtained from the bone marrow of CML patients at the onset of the disease, one year after the start of the treatment and during the long-term treatment with tyrosine kinase inhibitors (TKI).Materials and methods. The study involved an analysis of the characteristics of MMSCs, the concentration of CFU-Fs in the bone marrow of CML patients, as well as the relative expression level of genes (REL) associated with differentiation and involved in the regulation of haematopoiesis. The analysis was performed at the onset of the disease, one year after the start of the treatment, as well as 3–8 and 9–16 years after the TKI therapy. MMSCs and CFU-Fs of healthy donors were used for control purposes.Results. The concentration of CFU-Fs at the onset of the disease did not differ from that in donors; however, the relative expression level of genes associated with differentiation was increased in the CFU-F colonies. A year after the start of TKI treatment, the concentration of CFU-Fs decreased by four times. Subsequently, the concentration increased to reach normal values following 8 years of TKI treatment. The total production of MMSCs was not changed at the onset of the disease; however, it decreased after a year of TKI treatment, subsequently returning to normal. The expression of many genes was altered in the MMSCs of patients, i.e. the REL of LIF and JAG1 increased by 10 and 2 times, respectively; in the course of treatment, the REL of LIF in MMSCs decreased, always remaining higher than in those of the donors, whereas the expression of JAG1 returned to normal. At the onset of the disease, the REL of LIF in the MMSCs of patients, who achieved a deep molecular response (DMR) within 17 months of the treatment, was three times lower than in the MMSCs of those patients who did not reach DMR within 50 months, with JAG1 not differing from that of donors.Conclusion. Changes in stromal progenitor cells are associated with the influence of tumour cells, as well as with TKI therapy. A normal expression level of JAG1 and a decreased expression level of LIF in the MMSCs of CML patients at the onset of the disease may be predictive of DMR achievement.Conflict of interest: the authors declare no conflict of interest.Financial disclosure: the study had no sponsorship.