IL-7–dependent human leukemia T-cell line as a valuable tool for drug discovery in T-ALL

Barata, João T.; Boussiotis, Vassiliki A.; Yunes, José Andrés; Ferrando, Adolfo A.; Moreau, Lisa A.; Veiga, Joel Paulo Russomano; Sallan, Stephen E.; Look, A. Thomas; Nadler, Lee M.; Cardoso, Angelo A.

doi:10.1182/blood-2002-12-3861

Cited by 42 publications

(57 citation statements)

References 48 publications

(60 reference statements)

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“…Activation of the PI3K and Erk1/2 pathways in pre-T cells in response to IL-7 has not been previously evaluated (67). We found that IL-7 activated Akt and STAT5, as well as Erk1/2, which is in line with the finding that IL-7 activates Erk1/2 in an IL-7-dependent immature T cell line, TAIL-7 (68,69). Unlike STAT5 and Akt activation, both of which showed substantial increases upon IL-7 treatment, IL-7 activated Erk1/2 only in a small percentage of cells (ϳ8%), which correlated well with the marginal increase in CD25 expression in response to IL-7.…”

Section: Discussionsupporting

confidence: 81%

Synergistic Effects of Interleukin-7 and Pre-T Cell Receptor Signaling in Human T Cell Development

Patel

Chang

2012

Journal of Biological Chemistry

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Background:The role of IL-7 in human pre-T cell development is controversial. Results: Using IL-7R␣-modified Molt3, we demonstrate a synergistic effect of pre-TCR and IL-7 involving STAT5, Akt, and Erk1/2. Conclusion: There is a stringent requirement for down-regulation of IL-7/IL-7R␣ signaling during human T cell development. Significance: Understanding how IL-7 regulates human T cell development will help future development of T cell therapeutics.

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Section: Discussionsupporting

confidence: 81%

Synergistic Effects of Interleukin-7 and Pre-T Cell Receptor Signaling in Human T Cell Development

Patel

Chang

2012

Journal of Biological Chemistry

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“…Most prior studies have focused on signaling via IL-7 (Dibirdik et al, 1991;Barata et al, 2004aBarata et al, ,b,c, 2005González-Garcia et al, 2009;Shochat et al, 2011;Silva et al, 2011) or mutational activation of intermediates in the PI3K-Akt pathway Gutierrez et al, 2009). The importance of PI3K-Akt activation in T-ALL is underscored by multiple studies showing that PI3K-Akt/mTOR inhibitors block growth/survival of T-ALL cells (Avellino et al, 2005;Wei et al, 2006;Palomero et al, 2007;Chiarini et al, 2009;Cullion et al, 2009).…”

Section: Methodsmentioning

confidence: 99%

“…Although previous works have focused on the role of IL-7 signaling in T-ALL, including effects on downstream PI3K-Akt activation (Dibirdik et al, 1991;Barata et al, 2004aBarata et al, ,b,c, 2005González-Garcia et al, 2009;Shochat et al, 2011;Silva et al, 2011), we considered that insulin-like growth factor (IGF)-1 receptor (IGF1R) may also play an important role. IGFs and their receptors regulate normal cell growth and contribute to transformation and growth of malignant cells in many contexts (Pollak et al, 2004).…”

Section: Pharmacologic Inhibition Of Igf1r Compromises T-all Cell Growthmentioning

confidence: 99%

High-level IGF1R expression is required for leukemia-initiating cell activity in T-ALL and is supported by Notch signaling

Medyouf¹,

Gusscott²,

Wang³

et al. 2011

J Cell Biol

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“…TAIL7 cells share significant similarities with primary T-ALL samples. 18 In vitro culture IL-7-deprived TAIL7 cells or primary T-ALL cells were cultured as 2 Â 10treated for 30 min with H 2 O 2 and glucose oxidase to obtain steady-state levels of H 2 O 2 , as described. 19 Cells were then washed with phosphate-buffered saline and cultured under normal conditions for 48 h. Human peripheral blood mononuclear cells were cultured for 2 days with phorbol 12-myristate 13-acetate (10 ng/ml, Sigma-Aldrich) and ionomycin (1 mg/ml, Sigma-Aldrich), then washed and grown for at least 24 h in medium supplemented with 10 U/ml rhIL-2 (Roche Molecular Biochemicals, Mannheim, Germany).…”

Section: Cellsmentioning

confidence: 99%

Intracellular reactive oxygen species are essential for PI3K/Akt/mTOR-dependent IL-7-mediated viability of T-cell acute lymphoblastic leukemia cells

et al. 2011

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Interleukin-7 (IL-7) activates phosphoinositide 3-kinase/Akt/ mammalian target of rapamycin (PI3K/Akt/mTOR) pathway, thereby mediating viability, proliferation and growth of T-cell acute lymphoblastic leukemia (T-ALL) cells. Reactive oxygen species (ROS) can be upregulated by growth factors and are known to regulate proliferation and viability. Here, we show that IL-7 upregulates ROS in T-ALL cells in a manner that is dependent on PI3K/Akt/mTOR pathway activity and that relies on both NADPH oxidase and mitochondrial respiratory chain. Conversely, IL-7-induced activation of PI3K signaling pathway requires mitochondrial respiration and ROS. We have previously shown that IL-7-mediated activation of PI3K pathway drives the upregulation of the glucose transporter Glut1, promoting glucose uptake in T-ALL cells. Using phloretin to inhibit Glut function, we demonstrate that glucose uptake is mandatory for ROS upregulation in IL-7-treated T-ALL cells, suggesting that IL-7 stimulation leads to increased ROS via PI3K pathway activation and consequent upregulation of Glut1 and glucose uptake. Overall, our data reveal the existence of a critical crosstalk between PI3K/Akt signaling pathway and ROS that is essential for IL-7-mediated T-ALL cell survival, and that may constitute a novel target for therapeutic intervention.

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IL-7–dependent human leukemia T-cell line as a valuable tool for drug discovery in T-ALL

Cited by 42 publications

References 48 publications

Synergistic Effects of Interleukin-7 and Pre-T Cell Receptor Signaling in Human T Cell Development

Synergistic Effects of Interleukin-7 and Pre-T Cell Receptor Signaling in Human T Cell Development

High-level IGF1R expression is required for leukemia-initiating cell activity in T-ALL and is supported by Notch signaling

Intracellular reactive oxygen species are essential for PI3K/Akt/mTOR-dependent IL-7-mediated viability of T-cell acute lymphoblastic leukemia cells

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