Hypophosphorylation of pRB and repression of cyclin D3 and cdc25A during the granulocytic differentiation of human myeloblastic leukemia ML-1 cells

Shimizu, Takaki; Oka, Yuichi; Awai, Nao; Takeda, Ken

doi:10.1016/s0145-2126(99)00106-x

Cited by 8 publications

(5 citation statements)

References 27 publications

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“…These results indicate that ATRA and GM‐CSF in combination synergistically increase TPA‐stimulated superoxide production by ML‐1 cells. This observation agrees with our previous result of an NBT reducing assay (16).…”

Section: Resultssupporting

confidence: 94%

“…In general, retinoids do not promote granulocytic maturation in the subtypes of acute myeloid leukemia, except for APL. We recently induced ML‐1 cells to differentiate toward the granulocyte lineage by treatment with ATRA in combination with granulocyte macrophage colony‐stimulating factor (GM‐CSF) (15, 16). In this system, the superoxide‐generating activity of ML‐1 cells was increased synergistically by treatment with both reagents.…”

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confidence: 99%

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GM‐CSF induces expression of gp91^phox and stimulates retinoic acid‐induced p47^phox expression in human myeloblastic leukemia cells

Shimizu

Kodama

Tsunawaki³

et al. 2002

European J of Haematology

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All-trans retinoic acid (ATRA) combined with granulocyte macrophage colony-stimulating factor (GM-CSF) synergistically increases superoxide-generating activity in human myeloblastic leukemia ML-1 cells. ATRA is known to increase the expression of some NADPH components; however, little is known about the effect of GM-CSF on the expression of these components. We examined the expression of NADPH oxidase components in ML-1 cells treated with ATRA, GM-CSF, or a combination of ATRA and GM-CSF. Expression of p47phox and gp91phox proteins increased markedly after treatment with both reagents. p47phox expression was increased by ATRA alone, and the expression was increased synergistically by the combination of ATRA with GM-CSF. gp91phox was increased by ATRA or GM-CSF alone. The expression of p47phox and gp91phox mRNA underwent similar changes to those seen in protein level. These results indicate that GM-CSF induces expression of gp91phox and enhances ATRA-induced p47phox expression. We speculate that the remarkable induction of gp91phox and p47phox protein is associated with an increase in superoxide-generating activity due to the synergistic effect of ATRA plus GM-CSF.

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Section: Resultssupporting

confidence: 94%

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confidence: 99%

GM‐CSF induces expression of gp91^phox and stimulates retinoic acid‐induced p47^phox expression in human myeloblastic leukemia cells

Shimizu

Kodama

Tsunawaki³

et al. 2002

European J of Haematology

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“…However, it seems to be that ATRA is acting on the brakes, especially the INK4s and p21cip1 [7,10,11,59] (Fig. 4C) and through down-regulation of cyclins [9,60] rather than influencing CDK levels [12,60]. This resembles more the pattern seen in the reversible withdrawal of cells from the cell cycle, which is regulated by cytokines [4], than the irreversible cell-cycle stop seen, e.g., in terminally differentiated neurons [61].…”

Section: Discussionmentioning

confidence: 88%

End-stage differentiation of neutrophil granulocytes in vivo is accompanied by up-regulation of p27kip1 and down-regulation of CDK2, CDK4, and CDK6

Klausen

Bjerregaard

Borregaard

et al. 2003

Journal of Leukocyte Biology

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The in vivo expression profiles of cell-cycle proteins regulating G1-to-S-phase transition were determined in three neutrophil precursor populations from human bone marrow: myeloblasts (MBs) and promyelocytes (PMs); myelocytes (MCs) and metamyelocytes (MMs); and band cells (BCs) and segmented neutrophil cells (SCs) and in mature polymorphonuclear neutrophils (PMNs) from peripheral blood. Complete cell-cycle arrest was observed in BCs/SCs and PMNs. Cyclins D1, D2, and D3 were found to be down-regulated during granulopoiesis, whereas a slight increase of cyclin E was seen. In contrast, cyclin-dependent kinase (CDK)2, -4, and -6 were down-regulated from the MC/MM stages and onward. The transcript levels of CDK2, -4, and -6 were concurrently down-regulated. As the only CDK inhibitor, p27kip1 protein and mRNA expression were up-regulated in MCs/MMs and reached peak levels in PMNs. Protein expression of retinoblastoma protein and the related pocket proteins p107 and p130 was down-regulated from the MC/MM stages and onward. This is the first report to describe expression levels of cell-cycle proteins during granulopoiesis in vivo, and it strongly contrasts the observations made in cell-culture systems in vitro.

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“…The function of CDC25 also seems to be affected by AML cell differentiation, i.e., to differ between AML cells with no signs of differentiation and cells showing monocytic differentiation [49]. Similarly, CDC25 is downregulated when the monocytic AML cell line ML-1 is stimulated to differentiate towards granulocytes in vitro [155]. However, it is not known whether the limited signs of differentiation seen for primary AML cells will have any major impact on the level of CDC25 or the effects of CDC25 inhibition in vivo.…”

Section: Cdc25 and Induction Of Differentiation In Aml Cellsmentioning

confidence: 99%

Therapeutic Targeting the Cell Division Cycle 25 (CDC25) Phosphatases in Human Acute Myeloid Leukemia — The Possibility to Target Several Kinases through Inhibition of the Various CDC25 Isoforms

et al. 2014

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Abstract:The cell division cycle 25 (CDC25) phosphatases include CDC25A, CDC25B and CDC25C. These three molecules are important regulators of several steps in the cell cycle, including the activation of various cyclin-dependent kinases (CDKs). CDC25s seem to have a role in the development of several human malignancies, including acute myeloid leukemia (AML); and CDC25 inhibition is therefore considered as a possible anticancer strategy. Firstly, upregulation of CDC25A can enhance cell proliferation and the expression seems to be controlled through PI3K-Akt-mTOR signaling, a pathway possibly mediating chemoresistance in human AML. Loss of CDC25A is also important for the cell cycle arrest caused by differentiation induction of malignant hematopoietic cells. Secondly, high CDC25B expression is associated with resistance against the antiproliferative effect of PI3K-Akt-mTOR inhibitors in primary human AML cells, and inhibition of this isoform seems to reduce AML cell line proliferation through effects on NFκB and p300. Finally, CDC25C seems important for the phenotype of AML cells at least for a subset of patients. Many of the identified CDC25 inhibitors show cross-reactivity among the three CDC25 isoforms. Thus, by using such cross-reactive inhibitors it may become possible to inhibit OPEN ACCESSMolecules 2014, 19 18415 several molecular events in the regulation of cell cycle progression and even cytoplasmic signaling, including activation of several CDKs, through the use of a single drug. Such combined strategies will probably be an advantage in human cancer treatment.

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Hypophosphorylation of pRB and repression of cyclin D3 and cdc25A during the granulocytic differentiation of human myeloblastic leukemia ML-1 cells

Cited by 8 publications

References 27 publications

GM‐CSF induces expression of gp91^phox and stimulates retinoic acid‐induced p47^phox expression in human myeloblastic leukemia cells

GM‐CSF induces expression of gp91^phox and stimulates retinoic acid‐induced p47^phox expression in human myeloblastic leukemia cells

End-stage differentiation of neutrophil granulocytes in vivo is accompanied by up-regulation of p27kip1 and down-regulation of CDK2, CDK4, and CDK6

Therapeutic Targeting the Cell Division Cycle 25 (CDC25) Phosphatases in Human Acute Myeloid Leukemia — The Possibility to Target Several Kinases through Inhibition of the Various CDC25 Isoforms

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Hypophosphorylation of pRB and repression of cyclin D3 and cdc25A during the granulocytic differentiation of human myeloblastic leukemia ML-1 cells

Cited by 8 publications

References 27 publications

GM‐CSF induces expression of gp91phox and stimulates retinoic acid‐induced p47phox expression in human myeloblastic leukemia cells

GM‐CSF induces expression of gp91phox and stimulates retinoic acid‐induced p47phox expression in human myeloblastic leukemia cells

End-stage differentiation of neutrophil granulocytes in vivo is accompanied by up-regulation of p27kip1 and down-regulation of CDK2, CDK4, and CDK6

Therapeutic Targeting the Cell Division Cycle 25 (CDC25) Phosphatases in Human Acute Myeloid Leukemia — The Possibility to Target Several Kinases through Inhibition of the Various CDC25 Isoforms

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GM‐CSF induces expression of gp91^phox and stimulates retinoic acid‐induced p47^phox expression in human myeloblastic leukemia cells

GM‐CSF induces expression of gp91^phox and stimulates retinoic acid‐induced p47^phox expression in human myeloblastic leukemia cells