Evidence for a G2 checkpoint in p53-independent apoptosis induction by X-irradiation.

The p53 tumor suppressor gene is thought to be required for the induction of programmed cell death (apoptosis) initiated by DNA damage. We show here, however, that the human promyelocytic leukemia cell line HL-60, which is known to be deficient in p53 because of large deletions in the p53 gene, can be induced to undergo apoptosis following X-irradiation. We demonstrate that the decision to undergo apoptosis in this cell line appears to be made at a G2 checkpoint. In addition, we characterize an HL-60 variant, HCW-2, which is radioresistant. HCW-2 cells display DNA damage induction and repair capabilities identical to those of the parental HL-60 cell line. Thus, the difference between the two cell lines appears to be that X-irradiation induces apoptosis in HL-60, but not in HCW-2, cells. Paradoxically, HCW-2 cells display high levels of expression of bax, which enhances apoptosis, and no longer express bcl-2, which blocks apoptosis. HCW-2 cells' resistance to apoptosis may be due to the acquisition of expression of bcl-XL, a bcl-2-related inhibitor of apoptosis. In summary, apoptosis can be induced in X-irradiated HL-60 cells by a p53-independent mechanism at a G2 checkpoint, despite the presence of endogenous bcl-2. The resistance shown by HCW-2 cells suggests that bcl-XL can block this process.

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Establishment and Characterization of a New Ph1-Positive Chronic Myeloid Leukemia Cell Line MC3 with Trilineage Phenotype and an Altered p53 Gene

Leukemia & Lymphoma ◽

10.3109/10428199509054439 ◽

1995 ◽

Vol 16 (5-6) ◽

pp. 493-503 ◽

Cited By ~ 14

Author(s):

Mihiro Okabe ◽

Yasuyuki Kunieda ◽

Shingo Nakane ◽

Mitsutoshi Kurosawa ◽

Toshiyuki Itaya ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Cell Line ◽

Myeloid Leukemia ◽

Leukemia Cell ◽

P53 Gene ◽

Leukemia Cell Line ◽

Chronic Myeloid Leukemia Cell ◽

Myeloid Leukemia Cell

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Establishment and Characterization of a Human Acute Myelocytic Leukemic Cell Line, SH-2, Carrying t(16;17)(q24;q12).

Blood ◽

10.1182/blood.v108.11.4278.4278 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4278-4278

Author(s):

Hui Y. Qiu ◽

Yong Q. Xue ◽

Jin L. Pan ◽

Ya F. Wu ◽

Jun Zhang ◽

...

Keyword(s):

Cell Line ◽

Leukemia Cell ◽

Leukemic Cell ◽

P53 Gene ◽

Leukemia Cell Line ◽

Acute Myelocytic Leukemia ◽

Rt Pcr ◽

Leukemic Cell Line ◽

Myelocytic Leukemia

Abstract We present a novel human myeloid leukemic cell line, designated as SH-2 which was established from the bone marrow of a patient with acute myelocytic leukemia (AML-M2a) carrying t(16;17)(q24;q12) translocation. The cell line has proliferated continuously in vitro for more than 12 months. Its morphology showed typical features of acute myelocytic leukemia (AML). The cell line’s immunoprofile was accordant with AML (positivity for CD13, CD33, CD38, CD117, CD16, CD56 and MPO). Karyotypic analysis revealed the translocation t(16;17)(q24;q12), monosomy 17 and trisomy 19. The apoptosis related genes such as bcl-2, Fas and GST-πtranscription were detected by RT-PCR. Meanwhile, MDR1, MRP and LRP transcription were not detected by RT-PCR. The deletion of p53 gene and the translocation between chromosomes 16 and 17 were confirmed by FISH method. The SH-2 cells grew colonies in in vitro methylcellulose cultures. Tumor masses were found in 1/2 mice injected by the tail vein with the SH-2 cell line after two months. Infection of the EBV and the mycoplasma were also excluded. Cell line authentication by STR showed that the primary leukemia cell of the patient and the SH-2 cell line originated from same individual. SH-2 cells were proliferated by the addition of cytokines such as IL-3, GM-CSF and SCF. two point mutations in exon 5 of the p53 gene were detected in the SH-2 cells by PCR analysis and direct sequencing showing the conversion of T to G in both codon 349 and 417. The establishment of an myelocytic leukemia cell line with t(16;17)(q24;q12) could be valuable for the study of leukemogenesis and for the research of cloning the new gene involved in the t(16;17)(q24;q12) translocation.

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Ikaros Induces Quiescence and T-Cell Differentiation in a Leukemia Cell Line

Molecular and Cellular Biology ◽

10.1128/mcb.25.5.1645-1654.2005 ◽

2005 ◽

Vol 25 (5) ◽

pp. 1645-1654 ◽

Cited By ~ 52

Author(s):

Katie L. Kathrein ◽

Rachelle Lorenz ◽

Angela Minniti Innes ◽

Erin Griffiths ◽

Susan Winandy

Keyword(s):

Cell Cycle ◽

Cell Differentiation ◽

T Cell ◽

Tumor Suppressor ◽

Cell Line ◽

Tumor Suppressor Gene ◽

Leukemia Cell ◽

Suppressor Gene ◽

T Cell Differentiation ◽

Leukemia Cell Line

ABSTRACT Ikaros is a hematopoietic cell-specific zinc finger DNA binding protein that plays an important role in lymphocyte development. Genetic disruption of Ikaros results in T-cell transformation. Ikaros null mice develop leukemia with 100% penetrance. It has been hypothesized that Ikaros controls gene expression through its association with chromatin remodeling complexes. The development of leukemia in Ikaros null mice suggests that Ikaros has the characteristics of a tumor suppressor gene. In this report, we show that the introduction of Ikaros into an established mouse Ikaros null T leukemia cell line leads to growth arrest at the G0/G1 stage of the cell cycle. This arrest is associated with up-regulation of the cell cycle-dependent kinase inhibitor p27kip1, the induction of expression of T-cell differentiation markers, and a global and specific increase in histone H3 acetylation status. These studies provide strong evidence that Ikaros possesses the properties of a bona fide tumor suppressor gene for the T-cell lineage and offer insight into the mechanism of Ikaros's tumor suppressive activity.

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ALCAPs induce mitochondrial apoptosis and activate DNA damage response by generating ROS and inhibiting topoisomerase I enzyme activity in K562 leukemia cell line

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2011.05.078 ◽

2011 ◽

Vol 409 (4) ◽

pp. 738-744 ◽

Cited By ~ 22

Author(s):

Nuray Bogurcu ◽

Canan Sevimli-Gur ◽

Besra Ozmen ◽

Erdal Bedir ◽

Kemal Sami Korkmaz

Keyword(s):

Dna Damage ◽

Enzyme Activity ◽

Cell Line ◽

Dna Damage Response ◽

Topoisomerase I ◽

Leukemia Cell ◽

Leukemia Cell Line ◽

Mitochondrial Apoptosis ◽

Damage Response

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P53 Gene Mutation in a T-Acute Lymphoblastic Leukemia Cell Line (Loucy) with t(16:20) and 5q-Chromosomal Aberrations

Leukemia & Lymphoma ◽

10.3109/10428199809050920 ◽

1998 ◽

Vol 29 (5-6) ◽

pp. 607-611 ◽

Cited By ~ 4

Author(s):

Miron Prokocimer ◽

Shoshana Peller ◽

Hannah Ben-Bassat ◽

Naomi Goldfinger ◽

Varda Rotter

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Cell Line ◽

Gene Mutation ◽

Chromosomal Aberrations ◽

Lymphoblastic Leukemia ◽

Leukemia Cell ◽

P53 Gene ◽

Leukemia Cell Line ◽

P53 Gene Mutation ◽

Lymphoblastic Leukemia Cell Line

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Apoptotic Effects of a Thioether Analog of Vitamin K3 in a Human Leukemia Cell Line

International Journal of Toxicology ◽

10.1177/10915818211047992 ◽

2021 ◽

pp. 109158182110479

Author(s):

Satoru Asami ◽

Mikana Suzuki ◽

Toshimitsu Nakayama ◽

Yasuyo Shimoda ◽

Motofumi Miura ◽

...

Keyword(s):

Dna Damage ◽

Cell Line ◽

Vitamin K ◽

Caspase 3 ◽

Leukemia Cell ◽

Leukemia Cell Line ◽

Human Leukemia ◽

Potent Inducer ◽

Human Leukemia Cell ◽

Human Leukemia Cell Line

Research suggests that thioether analogs of vitamin K3 (VK3) can act to preserve the phosphorylation of epidermal growth factor receptors by blocking enzymes (phosphatases) responsible for their dephosphorylation. Additionally, these derivatives can induce apoptosis via mitogen-activated protein kinase and caspase-3 activation, inducing reactive oxygen species (ROS) production, and apoptosis. However, vitamin K1 exhibits only weak inhibition of phosphatase activity, while the ability of VK3 to cause oxidative DNA damage has raised concerns about carcinogenicity. Hence, in the current study, we designed, synthesized, and screened a number of VK3 analogs for their ability to enhance phosphorylation activity, without inducing off-target effects, such as DNA damage. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay revealed that each analog produced a different level of cytotoxicity in the Jurkat human leukemia cell line; however, none elicited a cytotoxic effect that differed significantly from that of the control. Of the VK3 analogs, CPD5 exhibited the lowest EC50, and flow cytometry results showed that apoptosis was induced at final concentrations of ≥10 μM; hence, only 0.1, 1, and 10 μM were evaluated in subsequent assays. Furthermore, CPD5 did not cause vitamin K-attributed ROS generation and was found to be associated with a significant increase in caspase 3 expression, indicating that, of the synthesized thioether VK3 analogs, CPD5 was a more potent inducer of apoptosis than VK3. Hence, further elucidation of the apoptosis-inducing effect of CPD5 may reveal its efficacy in other neoplastic cells and its potential as a medication.

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