ArticleLeukemia2000
Sensitisation of HL60 human leukaemic cells to cytotoxic drug-induced apoptosis by inhibition of PI3-kinase survival signals.
Article in Leukemia, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 81 citations in OpenAlex.
- Inhibition of PI3K Signaling Intensified the Antileukemic Effects of Pioglitazone: New Insight into the Application of PPARγ Stimulators in Acute Lymphoblastic Leukemia.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2023Article
- DeSUMOylation of chromatin-bound proteins limits the rapid transcriptional reprogramming induced by daunorubicin in acute myeloid leukemias.Nucleic acids research · 2023Article
- Targeting HDAC3, a new partner protein of AKT in the reversal of chemoresistance in acute myeloid leukemia via DNA damage response.Leukemia · 2017Article
- MK-2206 induces apoptosis of AML cells and enhances the cytotoxicity of cytarabine.Medical oncology (Northwood, London, England) · 2015Article
- Context-dependent antagonism between Akt inhibitors and topoisomerase poisons.Molecular pharmacology · 2014Article
- Chemical genomic screening identifies LY294002 as a modulator of glucocorticoid resistance in MLL-rearranged infant ALL.Leukemia · 2014Article
- A review of molecular mechanisms of the anti-leukemic effects of phenolic compounds in honey.International journal of molecular sciences · 2012Review
- Review
- Activity of any class IA PI3K isoform can sustain cell proliferation and survival.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Novel postremission strategies in adults with acute myeloid leukemia.Current opinion in hematology · 2009Review
- The phosphoinositide 3-kinase pathway in human cancer: genetic alterations and therapeutic implications.Current genomics · 2007Article
- Mapping genes that contribute to daunorubicin-induced cytotoxicity.Cancer research · 2007Article
- Generation of survival signal by differential interaction of p38MAPKalpha and p38MAPKbeta with caveolin-1 and caveolin-3 in the adapted heart.Journal of molecular and cellular cardiology · 2007Article
- NFV, an HIV-1 protease inhibitor, induces growth arrest, reduced Akt signalling, apoptosis and docetaxel sensitisation in NSCLC cell lines.British journal of cancer · 2006Article
- Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia.Leukemia · 2006Review
- Article
- Inhibition of phosphatidylinositol 3-kinase dephosphorylates BAD and promotes apoptosis in myeloid leukemias.Leukemia · 2004Article
- Constitutive NF-kappaB DNA-binding activity in AML is frequently mediated by a Ras/PI3-K/PKB-dependent pathway.Leukemia · 2004Article
- Vanillins--a novel family of DNA-PK inhibitors.Nucleic acids research · 2003Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug resistance remains a serious limiting factor in the treatment of acute myeloid leukaemia (AML) either at initial presentation or following primary or subsequent relapses. Using specific kinase inhibitors, this study has investigated the contribution of the Ras/PI3-kinase regulated survival pathways to drug resistance and suppression of apoptosis in a cell line derived from AML (HL60). Inhibition of the Raf/MAP-kinase (ERK) pathway with a specific MAP-kinase inhibitor, apigenin did not sensitise HL60 cells to drug-induced apoptosis, indicating a lack of involvement in chemoresistance. In contrast, the PI3-kinase inhibitors, LY294002 and wortmannin, did induce a significant increase in apoptosis in combination with cytotoxic drugs. The contribution of downstream mediators of PI3-kinase, p70S6-kinase and PKB/Akt were then investigated. While inhibition of p70S6-kinase with rapamycin did not increase drug-induced apoptosis, PI3-kinase inhibition resulted in notable dephosphorylation of PKB, suggesting that the PI3-kinase/PKB survival pathway may play a major role in chemoresistance in AML. This pathway has been reported to mediate heterodimer interactions with the proapoptotic regulator, Bad. In contrast to previous studies, we found no evidence of Bad binding to anti-apoptotic Bcl-2, Bcl-XL or McI-1, or of alterations in Bax heterodimers. This suggests that alternative targets of PI3-kinase/PKB, distinct from the Bcl-2 family may be responsible for contributing to survival factor-mediated drug resistance in AML.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.