Multipotent Mesenchymal Stromal Cells in Patients with Chronic Myeloid Leukemia before Discontinuation of Tyrosine Kinase Inhibitors
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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.
Key Wordschronic myeloid leukemia withdrawal syndrome molecular relapse multipotent mesenchymal stromal cells relative level of gene expression
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- 1.Aggoune D, Sorel N, Bonnet ML, Goujon JM, Tarte K, Hérault O, Domenech J, Réa D, Legros L, Johnson-Ansa H, Rousselot P, Cayssials E, Guerci-Bresler A, Bennaceur-Griscelli A, Chomel JC, Turhan AG. Bone marrow mesenchymal stromal cell (MSC) gene profiling in chronic myeloid leukemia (CML) patients at diagnosis and in deep molecular response induced by tyrosine kinase inhibitors (TKIs). Leuk. Res. 2017;60:94-102.CrossRefGoogle Scholar
- 3.Asano M, Umezu T, Katagiri S, Kobayashi C, Tauchi T, Gotoh M, Ando K, Okabe S, Ohyashiki JH, Ohyashiki K. Up-regulated exosomal miRNA-140-3p in CML patients with musculoskeletal pain associated with discontinuation of tyrosine kinase inhibitors. Int. J. Hematol. 2017;105(4):419-422.CrossRefGoogle Scholar
- 5.Efficace F, Baccarani M, Breccia M, Alimena G, Rosti G, Cottone F, Deliliers GL, Baratè C, Rossi AR, Fioritoni G, Luciano L, Turri D, Martino B, Di Raimondo F, Dabusti M, Bergamaschi M, Leoni P, Simula MP, Levato L, Ulisciani S, Veneri D, Sica S, Rambaldi A, Vignetti M, Mandelli F; GIMEMA. Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population. Blood. 2011;118(17):4554-4560.CrossRefGoogle Scholar
- 6.Iqbal N, Iqbal N. Imatinib: a breakthrough of targeted therapy in cancer. Chemother. Res. Pract. 2014;2014. ID 357027. doi: https://doi.org/10.1155/2014/357027.
- 7.Katagiri S, Tauchi T, Ando K, Okabe S, Gotoh M, Ohyashiki K. Low body weight and body mass index may be associated with musculoskeletal pain following imatinib discontinuation in chronic myeloid leukemia. Leuk. Res. Rep. 2017;7:33-35.Google Scholar
- 9.Kim TD, Rea D, Schwarz M, Grille P, Nicolini FE, Rosti G, Levato L, Giles FJ, Dombret H, Mirault T, Labussière H, Lindhorst R, Haverkamp W, Buschmann I, Dörken B, le Coutre PD. Peripheral artery occlusive disease in chronic phase chronic myeloid leukemia patients treated with nilotinib or imatinib. Leukemia. 2013;27(6):1316-1321.CrossRefGoogle Scholar
- 10.Laneuville P. When to stop tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia. Curr. Treat. Options in Oncol. 2018;19(3). ID 15. doi: https://doi.org/10.1007/s11864-018-0532-2.
- 11.Lee SE, Choi SY, Song HY, Kim SH, Choi MY, Park JS, Kim HJ, Kim SH, Zang DY, Oh S, Kim H, Do Y. R, Kwak JY, Kim JA, Kim DY, Mun YC, Lee WS, Chang MH, Park J, Kwon JH, Kim DW. Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study. Haematologica. 2016;101(6):717-723.CrossRefGoogle Scholar
- 12.Martignetti JA, Aqeel AA, Sewairi WA, Boumah CE, Kambouris M, Mayouf SA, Sheth KV, Eid WA, Dowling O, Harris J, Glucksman MJ, Bahabri S, Meyer BF, Desnick RJ. Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome. Nat. Genet. 2001;28(3):261-265.CrossRefGoogle Scholar
- 14.Richter J, Söderlund S, Lübking A, Dreimane A, Lotfi K, Markevärn B, Själander A, Saussele S, Olsson-Strömberg U, Stenke L. Musculoskeletal pain in patients with chronic myeloid leukemia after discontinuation of imatinib: a tyrosine kinase inhibitor withdrawal syndrome? J. Clin. Oncol. 2014;32(25):2821-2823.CrossRefGoogle Scholar