Features of the molecular expression of alkaline phosphatase gene in chronic myeloid leukemia

  • L. P. Shvachko
  • I. V. Kravchuk
  • G. D. Teleheiev


Aim. To study expression of alkaline phosphatase gene in chronic myeloid leukemia. Methods. Short-term primary cell culture, real-time PCR. Results. We have investigated the aberrant expression type ALP in CML progression. We have found that the intestinal type ALP is switched to germinal type embrional-like ALP in the patients with clinical CML progression (n=8) resulted from the sequencing analyse. Moreover, we have shown the interconnected epigenetic regulation of aberrant embrional-like type ALP and G-CSFR (granulocyte colony stimulation factor receptor) on the level of mRNA gene expression in CML patients under sodium butirate (HDACi) culture blood treatment (10 мМ). We have revealed simultaneously the epigenetic down-regulation mRNA gene expression of aberrant germinal GALP and up-regulation of G-CSFR by sodium butirate in CML progression. Conclusions. On the data obtained have been concluded that sodium butirate targeted induces the hemopoietic differentiation blood cell potential in CML pathogenesis by the G-CSF signaling pathway activation.

Keywords: CML, alkaline phosphatase, G-CSFR (granulocyte colony stimulation factor receptor), sodium butirate.


Millán J.L. Mammalian alkaline phosphatases: from biology to applications in medicine and biotechnology. Weinheim, Germany: Wiley-VCH Verlag GmbH, 2006. 337 p. doi: 10.1002/3527608060

Tsai L.Ch., Hung M.W., Chen Y.H., Su W.Ch., Chang G.G., Chang T.Ch. Expression and regulation of alkaline phosphatases in human breast cancer MCF-7 cells. Eur. J. Biochem. 2000. V. 267. P. 1330-1339. doi: 10.1046/j.1432-1327.2000.01100.x

Millan J.L. Multisystemic functions of alkaline phosphatases. Methods Mol Biol. 2013. V. 1053. P. 27-51. doi: 10.1007/978-1-62703-562-0_3

Linder C.H., Englund U.H., Narisawa S., Millan J.L., Magnusson P. Isozyme profile and tissue-origin of alkaline phosphatase in mouse serum. Bone. 2013. V. 53. P. 399-408. doi: 10.1016/j.bone.2012.12.048

Saif M.W., Alexander D.A., Wicox Ch.M. Serum Alkaline Phosphatase Level as a Prognostic Tool in Colorectal Cancer: A Study of 105 patients. J Appl Res. 2005. V. 5. P. 88-95.

Rao S.R., Snaith A.E., D.Marino D., Cheng X., Lwin S.T., Omiss I.R., Handy F.C., Edwards C.M. Tumour-derived alkaline phosphatase regula tes tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer. British Journal of Cancer. 2017. V. 116. P. 227-236. doi: 10.1038/bjc.2016.402

Schmittgen Th.D., Livak K.J. Analyzing real-time PCR data by the comparative Ct method. Nature Protocols. 2008. V. 3. P. 1101-1108. doi: 10.1038/nprot.2008.73

Christine B.Y., Peter A.J. Epigenetic therapy of cancer: past, present and future. Nature Reviews Drug Discovery. 2006. V. 5. P. 37-50. doi: 10.1038/nrd1930

Stengel K.R., Hiebert S.W. Class I HDACs Affect DNA Replication, Repair, and Chromatin Structure: Implications for Cancer Therapy. Antioxid Redox Signal. 2015. V. 23. P. 51-65. doi: 10.1089/ars.2014.5915

Olzscha H., Bekheet M.E., Sheikh S., La Thangue N.B. HDAC Inhibitors. Methods Mol Biol. 2016. V. 1436. P. 281-303. doi: 10.1007/978-1-4939-3667-0_19

Ahmadzadeh A., Khodadi E., Shahjahani M., Bertacchini J., Vosoughi T., Saki N. The Role of HDACs as Leukemia Therapy Targets using HDI. Int J Hematol Oncol Stem Cell Res. 2015. V. 9. P. 203-214.

Glass E., Viale P.H. Histone deacetylase inhibitors: novel agents in cancer treatment. Clin J Oncol Nurs. 2013. V. 17. P. 34-40. doi: 10.1188/13.CJON.34-40

Tsuji K., Ebihara Y. Expression of G-CSF receptor on myeloid progenitors. Leuk. Lymphoma. 2001. V. 42. P. 1351-1357. doi: 10.3109/10428190109097763

Sutherland J.A., Turner A.R., Mannoni P., McGann L.F., Ture J.M. Differentiation of K562 leukemia cells along erythroid, macrophage, and megakaryocyte lineages. J. Biol Responce Mod. 1986. V. 5. P. 250-262.