An update on allogeneic hematopoietic progenitor cell transplantation for myeloproliferative neoplasms in the era of tyrosine kinase inhibitors

Adekola, Kehinde; Popat, Uday; Ciurea, Stefan O.

doi:10.1038/bmt.2014.176

Cited by 9 publications

(6 citation statements)

References 50 publications

(87 reference statements)

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“…Previous studies have suggested that AMPK is a potential target that regulates various signaling pathways [ 32 ]. In addition, AMPK activators can suppress several types of tumors [ 33 ]. mTOR is known to play a central role in antitumor activity among the signaling pathways regulated by AMPK [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Propofol Inhibits HeLa Cells by Impairing Autophagic Flux via AMP-Activated Protein Kinase (AMPK) Activation and Endoplasmic Reticulum Stress Regulated by Calcium

Chen

Zhao

2018

Med Sci Monit

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BackgroundPropofol has antitumor effects against various cancers. However, the mechanism of action of propofol in HeLa human cervical cancer cells has not been elucidated.Material/MethodsWe treated HeLa human cervical cancer cells with different concentrations of propofol. Cell viability was evaluated with Cell Counting Kit-8 and apoptosis was analyzed by annexin V-fluorescein isothiocyanate and propidium iodide staining and flow cytometry. Autophagosome formation was evaluated based on microtubule-associated protein light chain (LC)3 conversion and light chain 3 puncta formation. Autophagosome clearance was assessed according to p62 protein level and autolysosome generation.ResultsWe found that propofol decreased cell viability and increased autophagosome generation in HeLa cells. Autophagosome formation was evaluated based on LC3 conversion and LC3 puncta formation. Autophagosome clearance was assessed according to p62 protein level. The AMPK/mTOR signaling pathway was found to be activated in propofol-induced autophagosome accumulation. Fluorescence analysis using LysoTracker dye revealed that propofol blocked autophagosome–lysosome fusion. Administration of rapamycin increased autophagosome clearance in propofol-treated HeLa cells. Additionally, propofol induced endoplasmic reticulum (ER) stress and disrupted intracellular Ca2+ balance, thereby enhancing autophagosome accumulation. Suppressing ER stress by treatment with tauroursodeoxycholic acid (TUDCA) enhanced these effects, suggesting that the cytotoxicity of propofol is related to induction of ER stress.ConclusionsThis study is the first to provide evidence that propofol-mediated autophagy regulation is an underlying part of the mechanism by which propofol regulates HeLa cells progression.

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Section: Discussionmentioning

confidence: 99%

Propofol Inhibits HeLa Cells by Impairing Autophagic Flux via AMP-Activated Protein Kinase (AMPK) Activation and Endoplasmic Reticulum Stress Regulated by Calcium

Chen

Zhao

2018

Med Sci Monit

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“…Therefore, tyrosine kinase inhibitors targeting the BCR-ABL fusion protein, including imatinib, dasatinib and nilotinib, are used for CML treatment, and have demonstrated improved outcomes in patients with CML (20). However, high relapse rates, drug resistance and high mortality rates associated with transplantation remain challenges for CML treatment (21).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have revealed that AMPK activators can suppress several types of tumors, including pancreatic, bladder and prostate cancer, through AMPK-dependent apoptosis (19)(20)(21). In addition, AMPK has been reported as a potential target that regulates various signaling pathways, subsequently exhibiting antileukemia activity (22).…”

Section: Discussionmentioning

confidence: 99%

Adenine causes cell cycle arrest and autophagy of chronic myelogenous leukemia K562 cells via AMP-activated protein kinase signaling

Chen

Lin

et al. 2017

Oncol Lett

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Abstract. AMP-activated protein kinase (AMPK) is known as a pivotal regulator of cellular metabolism. Mounting evidences have demonstrated that AMPK activation exerts tumor suppressive activity on leukemia cells. The present study reported that adenine, an AMPK activator, triggers cell cycle arrest and autophagy of human chronic myelogenous leukemia K562 cells consequently suppressing cell viability. The present findings revealed that adenine treatment (4.0-8.0 mM) significantly inhibited the viability of K562 cells to 69.3±2.5% (24 h) and 53.4±2.1% (48 h) of the control. Flow cytometric analysis revealed that there was a significant accumulation in G 2 /M phase, but not sub-G 1 phase K562 cells following exposure to adenine. Additional investigation demonstrated that adenine treatments significantly increased the number of acidic vesicular organelles and the level of autophagosomal microtubule associated protein 1 light chain 3 α (LC3) marker. By contrast, cleavage of caspase-9, caspase-3 and poly-ADPribose polymerase was insignificantly affected in K562 cells following adenine treatment. In K562 cells, adenine was able to markedly promote the phosphorylation of AMPKα and suppress the phosphorylation of mammalian target of rapamycin (mTOR), a downstream target of AMPK. In addition, inhibiting AMPK phosphorylation using dorsomorphin restored mTOR phosphorylation, inhibited the accumulation of LC3 and significantly recovered the suppressed cell viability in response to adenine. Taken together, the present results demonstrated that adenine induced G 2 /M phase arrest and autophagic cell death, consequently suppressing the viability of K562 cells, which may attribute to the AMPK activation triggered by adenine. These findings provide evidence that adenine may be beneficial to chronic myelogenous leukemia therapy by suppressing excessive cell proliferation.

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“…(2–9) However, allo-SCT for this disease has been associated with higher treatment-related mortality (TRM) and relapse rates, and, in general, worse outcomes than for other myeloproliferative neoplasms. (10) Data regarding allo-SCT outcomes in patients with CMML are currently limited to small retrospective series, and no prospective studies have been performed for CMML patients because of the relatively low number of patients with CMML treated with allogeneic transplantation. Moreover, timing of allo-SCT and benefit of induction therapy, in particular treatment with a hypomethylating agent before transplant, has not been studied.…”

Section: Introductionmentioning

confidence: 99%

Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Progression-Free Survival for Patients with Chronic Myelomonocytic Leukemia

Kongtim

Popat

Jiménez

et al. 2016

Biology of Blood and Marrow Transplantation

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The treatment of patients with chronic myelomonocytic leukemia (CMML) with transplant has not been optimized. We retrospectively reviewed the data for 83 consecutive patients with CMML (47 with CMML-1/2 and 36 with CMML progressed to acute myeloid leukemia) who received an allogeneic stem cell transplant at our institution between April 1991 and December 2013 to identify factors associated with improved survival and determine whether treatment with hypomethylating agents before transplant improves progression-free survival. The median age of the cohort was 57 years. Seventy-eight patients received induction treatment before transplant, with 37 receiving hypomethylating agents and 41 receiving cytotoxic chemotherapy. Patients treated with a hypomethylating agent had a significantly lower cumulative incidence of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; p=0.03), whereas TRM at 1 year post-transplant did not significantly differ between the groups (27% and 30%, respectively; p=0.84). The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a hypomethylating agent (43%) than in those treated with other agents (27%; p=0.04). Our data support the use of hypomethylating agents before allogeneic stem cell transplantation for patients with CMML to achieve morphologic remission and improve progression-free survival of these patients. Future studies are needed to confirm these findings.

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An update on allogeneic hematopoietic progenitor cell transplantation for myeloproliferative neoplasms in the era of tyrosine kinase inhibitors

Cited by 9 publications

References 50 publications

Propofol Inhibits HeLa Cells by Impairing Autophagic Flux via AMP-Activated Protein Kinase (AMPK) Activation and Endoplasmic Reticulum Stress Regulated by Calcium

Propofol Inhibits HeLa Cells by Impairing Autophagic Flux via AMP-Activated Protein Kinase (AMPK) Activation and Endoplasmic Reticulum Stress Regulated by Calcium

Adenine causes cell cycle arrest and autophagy of chronic myelogenous leukemia K562 cells via AMP-activated protein kinase signaling

Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Progression-Free Survival for Patients with Chronic Myelomonocytic Leukemia

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