Inhibition of poly(ADP-ribose) polymerase 1 protects against acute myeloid leukemia by suppressing the myeloproliferative leukemia virus oncogene

Oncotarget
Lingbo WangMingxiang Zhang

Abstract

An abnormal expression of poly(ADP-ribose) polymerase 1 (PARP-1) has been described in many tumors. PARP-1 promotes tumorigenesis and cancer progression by acting on different molecular pathways. PARP-1 inhibitors can be used with radiotherapy or chemotherapy to enhance the susceptibility of tumor cells to the treatment. However, the specific mechanism of PARP-1 in acute myeloid leukemia (AML) remains unknown. Our study showed that expression of PARP-1 was upregulated in AML patients. PARP-1 inhibition slowed AML cell proliferation, arrested the cell cycle, induced apoptosis in vitro and improved AML prognosis in vivo. Mechanistically, microarray assay of AML cells with loss of PARP-1 function revealed that the myeloproliferative leukemia virus oncogene (MPL) was significantly downregulated. In human AML samples, MPL expression was increased, and gain-of-function and loss-of-function analysis demonstrated that MPL promoted cell growth. Moreover, PARP-1 and MPL expression were positively correlated in AML samples, and their overexpression was associated with an unfavorable prognosis. Furthermore, PARP-1 and MPL consistently acted on Akt and ERK1/2 pathways, and the anti-proliferative and pro-apoptotic function observed with PARP...Continue Reading

References

Jun 10, 2000·Journal of Gastroenterology and Hepatology·F NomuraT Nakai
Oct 4, 2000·The Journal of Biological Chemistry·J M PleschkeF R Althaus
Jun 12, 2003·Annals of the New York Academy of Sciences·Kenneth Kaushansky
Jun 14, 2003·Leukemia Research·Sivatharsini ChelvatheebamPamela Greenwell
Mar 12, 2005·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·L YalcintepeE Bermek
Jun 17, 2005·Annals of the New York Academy of Sciences·Kenneth Kaushansky
Sep 9, 2005·Frontiers in Bioscience : a Journal and Virtual Library·David Santamaria, Sagrario Ortega
Jul 11, 2006·Nature Reviews. Molecular Cell Biology·Valérie SchreiberGilbert de Murcia
Dec 20, 2008·American Journal of Hematology·Rosa M AyalaFlorinda Gilsanz
Dec 25, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Rosa Quiles-PerezJavier Salmerón
Apr 22, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Peter C FongStan B Kaye
Jul 21, 2010·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C UnderhillH Bonnefoi
Mar 2, 2011·Journal of Cellular Biochemistry·Fu-Sheng Chou, James C Mulloy
Apr 16, 2011·Leukemia·L S SteelmanJ A McCubrey
Aug 19, 2011·Neuro-oncology·Stuart J SmithUNKNOWN Children's Cancer and Leukaemia Group Biological Studies Committee
Sep 13, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F RojoJ Albanell
Dec 14, 2011·Critical Reviews in Oncogenesis·Dan A LiebermannBarbara Hoffman
Apr 25, 2012·Hematology·Naval Daver, Jorge Cortes
Sep 18, 2012·Molecular and Cellular Endocrinology·Elisa LavaroneGiuseppe Damante
Nov 14, 2012·Expert Review of Hematology·Alison Walker, Guido Marcucci
Dec 27, 2012·Molecular Aspects of Medicine·Jana KrietschJean-Philippe Gagné
Jan 22, 2013·Current Opinion in Structural Biology·Marie-France Langelier, John M Pascal
Jan 29, 2013·Journal of Hematology & Oncology·Xin HeXiaoying Zhao
Jan 30, 2013·Molecular Aspects of Medicine·W Lee Kraus, Michael O Hottiger
Mar 16, 2013·Immunology·Maria Manuela RosadoClaudio Pioli
Mar 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jian Zhong TangWarren S Alexander
Jun 21, 2013·PLoS Genetics·María Isabel RodríguezF Javier Oliver
Jul 9, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kaiyu YuanYabing Chen
Aug 28, 2013·Molecular Cancer Therapeutics·Jeremy P H ChowRandy Y C Poon
Oct 3, 2013·Pathology Oncology Research : POR·Zeng Dong-FengKong Pei-Yan
Oct 4, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Partha MukhopadhyayPal Pacher
Jan 17, 2014·The Journal of Clinical Investigation·Dominique BluteauHana Raslova
Jan 24, 2014·Biochemical Society Transactions·Nicola Curtin
May 1, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F RojoJ Albanell

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Citations

Dec 2, 2015·Oncotarget·Wen-qian DongMing-xiang Zhang
May 31, 2018·Genetic Testing and Molecular Biomarkers·Hossein PashaiefarArdeshir Ghavamzadeh
May 26, 2018·Human Genome Variation·Hirokazu MorokawaTomoki Kosho
Jun 3, 2020·Blood Reviews·Claire FritzEunice S Wang
Feb 1, 2020·European Journal of Haematology·Nanami GotohHirokazu Murakami
Oct 16, 2021·Biomarkers in Medicine·Yan-Hua HuangGong-Hao He
Sep 17, 2021·Blood Advances·Christina-Nefeli KontandreopoulouNora-Athina Viniou

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Methods Mentioned

BETA
Flow
flow cytometry
Fluorescent
oncotherapy
density-gradient centrifugation
FACS

Software Mentioned

ImageJ
SPSS
ModFit LT

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