Bortezomib Mediated Downregulation of F-box Protein, S-phase Kinase-Associated Protein 2 (SKP2) Causes Apoptotic Cell Death in Chronic Myelogenous Leukemia Cells

Abstract A new human leukemia cell line, KT-1, was established from a patient in the blastic crisis phase of chronic myelogenous leukemia (CML). This cell line had a positive reaction for intracytoplasmic myeloperoxidase and two Philadelphia chromosomes (Ph1) [t(9;22)(q34;q11)] and lacked normal copies of chromosomes 9 and 22. Molecular characterization of the breakpoint in the t(9;22)(q34;q11) showed that KT-1 had a bcr-2/abl-2 splice junction. When the KT-1 cells were cultured with interferon (IFN)-α or IFN-γ, the growth of the cells were dose-dependently suppressed. IFN-α and IFN-γ exerted synergistic suppressive effects on the growth of KT-1 cells. Furthermore, IFN-α suppressed the expression of the bcr-ablfusion gene in KT-1 cells, and induced G1 cell-cycle arrest and apoptotic cell death. The KT-1 cell line should be a valuable tool for studying the molecular mechanism of the suppression of Ph1clone cells from CML by IFN.

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Interferon-alpha suppresses proliferation of chronic myelogenous leukemia cells K562 by extending cell cycle S-phase without inducing apoptosis

Blood Cells Molecules and Diseases ◽

10.1016/j.bcmd.2003.10.008 ◽

2004 ◽

Vol 32 (1) ◽

pp. 262-269 ◽

Cited By ~ 17

Author(s):

D GREBEOVA

Keyword(s):

Cell Cycle ◽

Chronic Myelogenous Leukemia ◽

Interferon Alpha ◽

S Phase ◽

Myelogenous Leukemia ◽

Leukemia Cells ◽

Chronic Myelogenous Leukemia Cells

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Suppression of Cell Proliferation and the Expression of abcr-abl Fusion Gene and Apoptotic Cell Death in a New Human Chronic Myelogenous Leukemia Cell Line, KT-1, by Interferon-α

Blood ◽

10.1182/blood.v91.2.641.641_641_648 ◽

1998 ◽

Vol 91 (2) ◽

pp. 641-648

Author(s):

Kohsuke Yanagisawa ◽

Hayato Yamauchi ◽

Masahiko Kaneko ◽

Hidehisa Kohno ◽

Hitoshi Hasegawa ◽

...

Keyword(s):

Cell Death ◽

Cell Line ◽

Chronic Myelogenous Leukemia ◽

Apoptotic Cell ◽

Leukemia Cell ◽

Apoptotic Cell Death ◽

Myelogenous Leukemia ◽

Leukemia Cell Line ◽

Human Leukemia ◽

Ifn Γ

A new human leukemia cell line, KT-1, was established from a patient in the blastic crisis phase of chronic myelogenous leukemia (CML). This cell line had a positive reaction for intracytoplasmic myeloperoxidase and two Philadelphia chromosomes (Ph1) [t(9;22)(q34;q11)] and lacked normal copies of chromosomes 9 and 22. Molecular characterization of the breakpoint in the t(9;22)(q34;q11) showed that KT-1 had a bcr-2/abl-2 splice junction. When the KT-1 cells were cultured with interferon (IFN)-α or IFN-γ, the growth of the cells were dose-dependently suppressed. IFN-α and IFN-γ exerted synergistic suppressive effects on the growth of KT-1 cells. Furthermore, IFN-α suppressed the expression of the bcr-ablfusion gene in KT-1 cells, and induced G1 cell-cycle arrest and apoptotic cell death. The KT-1 cell line should be a valuable tool for studying the molecular mechanism of the suppression of Ph1clone cells from CML by IFN.

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