Role and mechanism of decitabine combined with tyrosine kinase inhibitors in advanced chronic myeloid leukemia cells

Jiang,Li‑Cai; Luo,Jian‑Min

doi:10.3892/ol.2017.6318

Role and mechanism of decitabine combined with tyrosine kinase inhibitors in advanced chronic myeloid leukemia cells

Authors:
- Li‑Cai Jiang
- Jian‑Min Luo
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Affiliations: Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
Published online on: June 6, 2017 https://doi.org/10.3892/ol.2017.6318
Pages: 1295-1302
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Patients with advanced chronic myeloid leukemia (CML) have a poor prognosis, with the use of tyrosine kinase inhibitors (TKIs) to treat CML demonstrating poor results. The results of the present study revealed that, following Cell Counting Kit-8 analysis, treatment of K562 cells with decitabine (DAC) combined with TKIs exhibits synergic effects. Co‑immunoprecipitation indicated that tyrosine‑protein phosphatase non‑receptor type 6 (SHP‑1) and BCR‑ABL fusion protein (BCR‑ABL) (p210) form a complex in the K562 cell line, and in the primary cells derived from patients with CML. These results suggested that SHP‑1 serves a role in regulating the tyrosine kinase activity of BCR‑ABL (p210). In addition, SHP‑1 expression increased, while BCR‑ABL expression decreased in the group treated with DAC and TKIs combined group compared with the TKI monotherapy group. Treatment with imatinib (IM) demonstrated no effect on SHP‑1 methylation in the K562 cell line; however, the methylation of SHP‑1 was not determined in the combined IM and DAC therapy group. Treatment with DAC demonstrated the ability to activate the expression of silenced SHP‑1 through demethylation, thus decreasing BCR-ABL tyrosine kinase activity, resulting in an improved therapeutic effect on CML.

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