title: Knockdown of Peripheral Myelin Protein 22 Inhibits the Progression of Chronic Myeloid Leukemia.
abstract: We aimed to explore the underlying mechanism of peripheral myelin protein 22 (PMP22) in the development of chronic myeloid leukemia (CML). The level of PMP22 expression in CD34(+) cells isolated from CML patients' bone marrow samples (BMMCs) and peripheral blood samples (PBMCs) was determined by RT-PCR. In addition, PMP22-siRNA and scrambled control siRNA were transfected into human CML cell line K562 with Lipofectamine 2000 reagent. Cell viability and apoptosis were, respectively, determined by MTT assay and flow cytometry. Besides, the level of caspase 3 and Bcl-xL was then detected using Western blot. The level of PMP22 expression in CML patients' CD34(+) cells isolated from both PBMCs and BMMCs was significantly higher than the control group. PMP22 expression in K562 cells was successfully knocked down by siRNA. MTT analysis showed that knockdown of PMP22 inhibited the proliferation of CML cells. Flow cytometry showed that knockdown of PMP22 promoted the apoptosis of CML cells. Besides, Bcl-xL expression markedly decreased, while the expression of caspase 3 in CML cells significantly increased after knockdown of PMP22 expression. Our findings indicate that high expression of PMP22 may promote cell proliferation and inhibit cell apoptosis via upregulation of Bcl-xL or inhibition of caspase 3 activation, and thus may contribute to the development of CML. PMP22 may serve as a novel therapeutic target for the treatment of CML.
authors.affiliation: Department of Hematology, The Affiliated Hospital of Yan'an University, Yan'an, Shanxi, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Hui-qin
authors.initials: HQ
authors.lastname: Cao
authors.forename: Jin-bao
authors.initials: JB
authors.lastname: Ta
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Yu-hong
authors.initials: YH
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D018450:Disease Progression; D055785:Gene Knockdown Techniques; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D009185:Myelin Proteins / Q000172:deficiency* / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human