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

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.

SUBMITTER: Jiang LC

PROVIDER: S-EPMC5529866 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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