Multipotent Mesenchymal Stromal Cells in Patients with Chronic Myeloid Leukemia before Discontinuation of Tyrosine Kinase Inhibitors

• Published in: Bulletin of experimental biology and medicine Vol. 167; no. 4; pp. 580 - 583
• Main Authors: Petinati, N. A., Petrova, A. N., Chelysheva, E. Yu, Shukhov, O. A., Bykova, A. V., Nemchenko, I. S., Sats, N. V., Turkina, A. G., Drize, N. I.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2019; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Biomedical and Life Sciences; Biomedicine; Body weight; Care and treatment; Cell Biology; Chronic myeloid leukemia; Female; Fibroblast growth factor receptor 2; Gelatinase A; Gene expression; Genes; Humans; Internal Medicine; Laboratory Medicine; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Male; Mesenchymal stem cells; Mesenchymal Stem Cells - pathology; Mesenchyme; Middle Aged; Myeloid leukemia; Pathology; Phenols; Platelet-derived growth factor; Protein Kinase Inhibitors - therapeutic use; Sox9 protein; Stem cells; Stromal cells; Substance Withdrawal Syndrome - pathology; Tyrosine; Tyrosine kinase inhibitors; Young Adult; withdrawal syndrome; relative level of gene expression; chronic myeloid leukemia; molecular relapse; multipotent mesenchymal stromal cells
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-019-04575-0

We analyzed changes in multipotent mesenchymal stromal cells of patients with chronic myeloid leukemia before discontinuation of tyrosine kinase inhibitors. Withdrawal syndrome was significantly more common in patients who have been taking tyrosine kinase inhibitors for a longer time and in patients of older age and with lower body weight. In patients with withdrawal syndrome, the total production of mesenchymal stromal cells and expression of FGFR2 and MMP2 genes were significantly lower; loss of deep molecular response was also less frequent in this group of patients. At the same time, the expression of genes important for the maintenance of stem cells ( SOX9 , PDGFRa , and LIF ) was significantly lower in the mesenchymal stromal cells of patients with withdrawal syndrome and loss of deep molecular response. We observed a clear-cut relationship between the development of withdrawal syndrome and the loss of deep molecular response. The decrease in the expression of FGFR2 and MMP2 genes in the mesenchymal stromal cells of patients with chronic myeloid leukemia before discontinuation of treatment can be a predictor of withdrawal syndrome, while simultaneous decrease in the expression of SOX9 , PDGFRa , and LIF in these cells attests to undesirability of therapy discontinuation at the moment.