The effect of steroid on myeloid leukemic cells: The potential of short-course high-dose methylprednisolone treatment in inducing differentiation, apoptosis and in stimulating myelopoiesis

Hiçsönmez, G

doi:10.1016/j.leukres.2005.05.015

Cited by 31 publications

(17 citation statements)

References 83 publications

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“…Although chemotherapy is most frequently used in leukemia treatment, it has been associated with many side effects such as systemic cytotoxicity and multi-drug resistance [1–3]. To overcome such problems, various anti-cancer drugs have been applied in combination or given together with substances that increase sensitivity of leukemia cells to chemotherapy such as butyrate [4].…”

Section: Introductionmentioning

confidence: 99%

Ethyl Pyruvate Combats Human Leukemia Cells but Spares Normal Blood Cells

et al. 2016

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Ethyl pyruvate, a known ROS scavenger and anti-inflammatory drug was found to combat leukemia cells. Tumor cell killing was achieved by concerted action of necrosis/apoptosis induction, ATP depletion, and inhibition of glycolytic and para-glycolytic enzymes. Ethyl lactate was less harmful to leukemia cells but was found to arrest cell cycle in the G0/G1 phase. Both, ethyl pyruvate and ethyl lactate were identified as new inhibitors of GSK-3β. Despite the strong effect of ethyl pyruvate on leukemia cells, human cognate blood cells were only marginally affected. The data were compiled by immune blotting, flow cytometry, enzyme activity assay and gene array analysis. Our results inform new mechanisms of ethyl pyruvate-induced cell death, offering thereby a new treatment regime with a high therapeutic window for leukemic tumors.

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Section: Introductionmentioning

confidence: 99%

Ethyl Pyruvate Combats Human Leukemia Cells but Spares Normal Blood Cells

et al. 2016

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“…83 In patients with initial neutropenia or hypoplastic bone marrow, accelerated recovery of peripheral blood leukocytes with MDMP was also noted. 84,85 The bone marrow protective effect of dexamethasone in murine leukemia supports these observations. 86 In a previously designed AML protocol in our clinic, MDMP was used as a differentiation inducer and was compared with conventional dose steroids.…”

Section: Acute Myeloblastic Leukemiamentioning

confidence: 63%

“…87 Better results in AML were obtained with MDMP, not only in newly diagnosed cases, but also in those in relapse who had not received MDMP previously. 85 It is known that GCs exert their cytotoxic effect through the induction of apoptosis. GC resistance has an adverse impact on clinical outcome in childhood leukemia.…”

Section: Acute Myeloblastic Leukemiamentioning

confidence: 99%

Comparison of Megadose Methylprednisolone Versus Conventional Dose Prednisolone in Hematologic Disorders

Yetgin

Özsoylu²

2007

Journal of Pediatric Hematology/Oncology

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Glucocorticoids (GCs) are known for their clinically useful effects in immunologic and inflammatory disorders. Although there is a huge volume of knowledge concerning the cellular and molecular effects of GCs, statements regarding their effects in multiple diseases at variable doses are not clear-cut owing to pharmacogenetic differences. The main actions of GCs in hematologic disorders have been related to their differentiation-inducing and apoptosis-inducing effects, but modification of several steps of the hematopoietic and/or immune pathway has also been reported. In our clinic, mega-dose methylprednisolone (MDMP) has been successfully used for treatment of different hematologic diseases, such as leukemias, bone marrow failure in aplastic anemia, hypoplastic anemia, myelodysplastic syndrome, neutropenia, autoimmune diseases, and in some congenital hereditary diseases. Both clinical and experimental studies in our department revealed that MDMP was more effective than conventional dose steroids. It is interesting that MDMP can be curative in some congenital hereditary diseases such as Diamond-Blackfan syndrome. However, more research is required to clarify their roles in biology, physiology, and molecular genetics.

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“…GC-mediated induction of GILZ also modulated the mTORC2/AKT/FoxO3a/Bim pathway. Although their effects have been more widely studied in lymphoid cells, GCs can also induce cell death or differentiation in the myeloid–monocyte lineage and have been shown to induce apoptosis in AML cells, including BCR-ABL + cells (Miyoshi et al , 1997; Schmidt et al , 2001; Dayyani et al , 2003; Hicsonmez, 2006). Although several pathways may be responsible for GC-induced apoptosis in myeloid cells, our results suggest that GILZ may have a role in vivo , at least in BCR-ABL + cells.…”

Section: Discussionmentioning

confidence: 99%

GILZ inhibits the mTORC2/AKT pathway in BCR-ABL+ cells

et al. 2011

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The malignant phenotype of chronic myeloid leukemia (CML) is due to the abnormal tyrosine kinase activity of the BCR-ABL oncoprotein, which signals several downstream cell survival pathways, including phosphoinositide 3-kinase/AKT, signal transducer and activator of transcription 5 and extracellular signal-regulated kinase 1/2. In patients with CML, tyrosine kinase inhibitors (TKIs) are used to suppress the BCR-ABL tyrosine kinase, resulting in impressive response rates. However, resistance can occur, especially in acute-phase CML, through various mechanisms. Here, we show that the glucocorticoid-induced leucine zipper protein (GILZ) modulates imatinib and dasatinib resistance and suppresses tumor growth by inactivating the mammalian target of rapamycin complex-2 (mTORC2)/AKT signaling pathway. In mouse and human models, GILZ binds to mTORC2, but not to mTORC1, inhibiting phosphorylation of AKT (at Ser473) and activating FoxO3a-mediated transcription of the pro-apoptotic protein Bim; these results demonstrate that GILZ is a key inhibitor of the mTORC2 pathway. Furthermore, CD34+ stem cells isolated from relapsing CML patients underwent apoptosis and showed inhibition of mTORC2 after incubation with glucocorticoids and imatinib. Our findings provide new mechanistic insights into the role of mTORC2 in BCR-ABL+ cells and indicate that regulation by GILZ may influence TKI sensitivity.

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The effect of steroid on myeloid leukemic cells: The potential of short-course high-dose methylprednisolone treatment in inducing differentiation, apoptosis and in stimulating myelopoiesis

Cited by 31 publications

References 83 publications

Ethyl Pyruvate Combats Human Leukemia Cells but Spares Normal Blood Cells

Ethyl Pyruvate Combats Human Leukemia Cells but Spares Normal Blood Cells

Comparison of Megadose Methylprednisolone Versus Conventional Dose Prednisolone in Hematologic Disorders

GILZ inhibits the mTORC2/AKT pathway in BCR-ABL+ cells

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