Differential gene expression changes and their implication on the disease progression in patients with Chronic Myeloid Leukemia

Chandran, Ramachandran Krishna; Narayanan, Geetha; Sakthivel, Kunnathur Murugesan; Kumar, Raveendran Suresh; Krishna, Kumarapillai Mohanan Nair Jagathnath; Subramanian, Hariharan

doi:10.1016/j.bcmd.2019.03.004

Cited by 4 publications

(2 citation statements)

References 46 publications

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“…C-myc gene expression was abnormally increased in different stages of CML: The levels in the blast phase were significantly higher than the accelerated phase, and the blast phase and the accelerated phase were markedly higher than the chronic phase and the control group. This result suggested that the high expression of C-myc gene may be one of the mechanisms of the progression and blast crisis of CML [ 19 ]. Additionally, tetrandrine can effectively induce leukemia cell differentiation and autophagy, and both ROS generation and C-myc inhibition are of pivotal significance in the process of autophagy and differentiation induced by tetrandrine [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Effects of 2-Methoxyestradiol (Hypoxia-Inducible Factor 1α Inhibitor) and Dasatinib (A Second-Generation Tyrosine Kinase Inhibitor) on Chronic Myelocytic Leukemia Cells

Zhang

Chen

Shen

et al. 2022

Journal of Immunology Research

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Chronic myelocytic leukemia (CML) is a frequently encountered type of leukemia in China. Hypoxia-inducible factor 1 (HIF-1) serves as one of the most important factors of oxygen balance transcription. The activation of this gene mostly marks a poor outlook for cancer patients. To clarify the therapeutic effect of inhibiting this gene on CML, the present study is aimed at exploring the treatment effects of 2-methoxyestradiol (2-ME2), dasatinib alone, and combined both on K-562 cells and the possible mechanism of 2-ME2 in treating the disorder. The levels of HIF-1α, vascular endothelial growth factor (VEGF), and glutamate synthase 1 (GLU1) genes in K-562 cells were affected dose-dependently after 2-ME2 administration. 2-ME2 induced cell apoptosis by downregulating antiapoptotic protein expressions of Bcl-xl and Bcl-2. The therapeutic effect of single 2-ME2 was superior to single dasatinib, and the effect of combined therapy of both drugs produced better effectiveness than either of the single drug. Once the concentration of 2-ME2 exceeded 0.5 μM, downregulated C-myc gene expression could exert roles in anti-CML cell proliferation and inducing apoptosis. Dasatinib might participate in the inhibition of the C-myc pathway during this process whereas its effect remained not clear. Taken together, abnormal high expression of HIF-1α exerted an essential role in CML occurrence and development. Inhibition of this gene could markedly increase cell apoptosis in a dose-dependent fashion. Moreover, 2-ME2 could induce cell apoptosis by downregulating the C-myc gene and exert an apoptotic effect by downregulating Bcl-xl and Bcl-2 which act as antiapoptotic proteins.

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Section: Discussionmentioning

confidence: 99%

Combined Effects of 2-Methoxyestradiol (Hypoxia-Inducible Factor 1α Inhibitor) and Dasatinib (A Second-Generation Tyrosine Kinase Inhibitor) on Chronic Myelocytic Leukemia Cells

Zhang

Chen

Shen

et al. 2022

Journal of Immunology Research

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“…found that differential gene expression changes are associated with TKI resistance and disease progression in CML. 24 Overexpression of c-MYC, down-regulation of ABCB1, BCL-2 and BAD, and complex interactions of several candidate genes such as C/EBPα/-β play an important role in the evolution and development of drug resistance in CML. In addition, other scholars explore the resistance and countermeasures of CML from the perspective of cytokines.…”

Section: Discussionmentioning

confidence: 99%

<p>Protective autophagy or autophagic death: effects of BEZ235 on chronic myelogenous leukemia</p>

Xin¹,

Xu²,

Zhu³

et al. 2019

CMAR

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Purpose: To investigate the effects of BEZ235 on chronic myeloid leukemia (CML) cells. Methods: MTS assay was used to detect the proliferation of CML cells. The proteins expression were detected by Western blot assay. The effects of BEZ235 on autophagy in CML cells were verified through transmission electron microscopy and evaluated by laser confocal microscopy. Annexin V-FITC/PI double staining flow cytometry was used to detect apoptosis. A xenograft model was established to observe the therapeutic effect of BEZ235 in vivo. Results: BEZ235 could inhibit the proliferation of CML cells; CQ and 3-MA could increase the proliferation inhibition and Z-VAD-FMK can reduce the proliferation inhibition of BEZ235 on CML cells (P<0.05). Results of TEM showed that the autophagosomes of CML cells treated with BEZ235 increased (P<0.05). The results by confocal microscopy showed that the autophagic activity of K562 cells increased with BEZ235 treatment. When BEZ235 combined with CQ, BEZ235-induced autophagic flow was blocked. FCM results showed that BEZ235 could induces apoptosis in CML cells. Z-VAD-FMK could decrease the apoptosis of CML cells induced by BEZ235. CQ increased the apoptosis of CML cells induced by BEZ235 (P<0.05). Western blot showed that BEZ235 inhibited the phosphorylation of AKT and S6K. BEZ235 alone could upregulate the expression of cleaved caspase-3 and LC3II. When combined with Z-VAD-FMK, the expression of cleaved caspase-3 was lower than that of BEZ235 alone. When combined with CQ, the expression of cleaved caspase-3 and LC3II were higher than those of BEZ235 alone (P<0.05). BEZ235 could inhibit the growth of xenografts of CML cell line. Conclusion: BEZ235 can inhibit the proliferation of CML cells, induce apoptosis, and enhance autophagy activity. It induces protective autophagy. The combination of CQ can enhance the apoptosis and proliferation inhibition of CML cells induced by BEZ235.

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Hsa_circ_0006010 and hsa_circ_0002903 in peripheral blood serve as novel diagnostic, surveillance and prognostic biomarkers for disease progression in chronic myeloid leukemia

Zhao,

Wang,

Yan

et al. 2024

BMC Cancer

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Differential gene expression changes and their implication on the disease progression in patients with Chronic Myeloid Leukemia

Cited by 4 publications

References 46 publications

Combined Effects of 2-Methoxyestradiol (Hypoxia-Inducible Factor 1α Inhibitor) and Dasatinib (A Second-Generation Tyrosine Kinase Inhibitor) on Chronic Myelocytic Leukemia Cells

Combined Effects of 2-Methoxyestradiol (Hypoxia-Inducible Factor 1α Inhibitor) and Dasatinib (A Second-Generation Tyrosine Kinase Inhibitor) on Chronic Myelocytic Leukemia Cells

<p>Protective autophagy or autophagic death: effects of BEZ235 on chronic myelogenous leukemia</p>

Hsa_circ_0006010 and hsa_circ_0002903 in peripheral blood serve as novel diagnostic, surveillance and prognostic biomarkers for disease progression in chronic myeloid leukemia

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