Targeting Aberrant Epigenetic Networks Mediated by PRMT1 and KDM4C in Acute Myeloid Leukemia

Cancer Cell
Ngai CheungChi Wai Eric So

Abstract

Transcriptional deregulation plays a major role in acute myeloid leukemia, and therefore identification of epigenetic modifying enzymes essential for the maintenance of oncogenic transcription programs holds the key to better understanding of the biology and designing effective therapeutic strategies for the disease. Here we provide experimental evidence for the functional involvement and therapeutic potential of targeting PRMT1, an H4R3 methyltransferase, in various MLL and non-MLL leukemias. PRMT1 is necessary but not sufficient for leukemic transformation, which requires co-recruitment of KDM4C, an H3K9 demethylase, by chimeric transcription factors to mediate epigenetic reprogramming. Pharmacological inhibition of KDM4C/PRMT1 suppresses transcription and transformation ability of MLL fusions and MOZ-TIF2, revealing a tractable aberrant epigenetic circuitry mediated by KDM4C and PRMT1 in acute leukemia.

References

Mar 1, 2002·The New England Journal of Medicine·Hagop KantarjianUNKNOWN International STI571 CML Study Group
Apr 27, 2005·Cell·Yuki OkadaYi Zhang
Aug 2, 2005·Molecular and Cellular Biology·Robert J InghamTony Pawson
Aug 5, 2005·Nature·Melanie BraigClemens A Schmitt
May 17, 2006·Genes & Development·Takuo KatsumotoIssay Kitabayashi
May 26, 2006·The American Journal of Pathology·Christian M BeckerRobert J D'Amato
Feb 27, 2007·Cell·Tony Kouzarides
Sep 25, 2007·Nature Cell Biology·Ngai CheungChi Wai Eric So
May 18, 2010·International Journal of Cancer. Journal International Du Cancer·Masanori YoshimatsuRyuji Hamamoto
Dec 16, 2010·Cancer Cell·Lixin RuiLouis M Staudt
Jan 14, 2011·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Konstantina MathioudakiMaroulio Talieri
Apr 12, 2011·FEBS Letters·Ngai Cheung, Chi Wai Eric So
Aug 18, 2012·Nature Reviews. Cancer·Alan H ShihRoss L Levine
Oct 2, 2012·Nature Chemical Biology·Sarah K KnutsonKevin W Kuntz
Nov 17, 2012·Cancer Cell·Bernd B ZeisigChi Wai Eric So
Nov 30, 2012·The New England Journal of Medicine·Jorge E CortesMoshe Talpaz
Mar 23, 2013·Cancer Cell·Maria Francisca ArteagaChi Wai Eric So
Jul 12, 2013·The New England Journal of Medicine·Francesco Lo-CocoUNKNOWN Study Alliance Leukemia
Jan 3, 2014·The Journal of Clinical Investigation·Robert M Campbell, Peter J Tummino
Jan 8, 2014·Molecular and Cellular Biology·Marianne Terndrup PedersenKristian Helin
Feb 7, 2014·Blood·Patrycja SroczynskaKristian Helin
May 23, 2014·Drug Discovery Today. Technologies·Stefan BalabanovTim H Brümmendorf
Jun 15, 2014·Proceedings of the National Academy of Sciences of the United States of America·Chunyu JinMichael G Rosenfeld
Jul 21, 2015·Cancer Cell·Stephen H K WongMichael L Cleary

❮ Previous
Next ❯

Citations

Mar 31, 2016·Experimental Hematology·Sarah M GreenblattStephen D Nimer
Jun 28, 2016·Cell Reports·Naidu M VegiChristian Buske
Nov 20, 2016·Experimental Hematology·Laura GodfreyThomas A Milne
Jan 4, 2017·Expert Review of Proteomics·Chao Peng, Catherine Cl Wong
Jan 7, 2017·Epigenetics : Official Journal of the DNA Methylation Society·Eleonore Maury, Rintaro Hashizume
May 16, 2017·Genes·Candace J Poole, Jan van Riggelen
May 22, 2018·Expert Opinion on Therapeutic Targets·Emily SmithRobert A Baiocchi
Sep 28, 2018·Journal of Cellular Biochemistry·Cigir Biray AvciCumhur Gunduz
Feb 14, 2019·Expert Opinion on Therapeutic Targets·Tyler S McCannPaul Jedlicka
May 20, 2018·Nature Communications·Anna SkuchaFlorian Grebien
Sep 22, 2017·Current Medicinal Chemistry·Yinglu LiWei-Guo Zhu
Jun 20, 2019·Cancers·Mélanie LambertMarie-Hélène David-Cordonnier
Oct 6, 2017·The EMBO Journal·Teerapong SiriboonpiputtanaChi Wai Eric So
Sep 4, 2019·Molecular Carcinogenesis·Changbao ChenXinlong Ma
Jan 22, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dong Hoon LeeSo Hee Kwon
Dec 7, 2017·Oncotarget·Chengcheng ZhangQi Li
Aug 14, 2020·Chembiochem : a European Journal of Chemical Biology·Jenna N BeyerGeorge M Burslem
Oct 5, 2019·Nature Structural & Molecular Biology·Konstantinos TzelepisTony Kouzarides
Nov 5, 2019·Frontiers in Cell and Developmental Biology·Valentina GambacortaRaffaella Di Micco
Jun 27, 2017·MedChemComm·Jing ZhangYujun George Zheng
Jun 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mélanie LambertMarie-Hélène David-Cordonnier
Nov 18, 2018·Cellular Oncology (Dordrecht)·Xin Xu, Björn Schneider
Jul 28, 2019·Nature Reviews. Molecular Cell Biology·Ernesto Guccione, Stéphane Richard
Oct 3, 2019·International Journal of Molecular Sciences·Jin Wook HwangAli G Turhan
Apr 21, 2018·Blood·David M Heery
Sep 26, 2019·Frontiers in Oncology·Bettina Wingelhofer, Tim C P Somervaille
Oct 11, 2017·Annual Review of Pharmacology and Toxicology·Richard L Bennett, Jonathan D Licht
Aug 10, 2019·Blood·Kira Gritsman

❮ Previous
Next ❯

Methods Mentioned

BETA
pull-down
immunoprecipitation assay
immunoprecipitation
ChIP
co-immunoprecipitation
acetylation
Xenograft
dissection
PCR
genotyping

Software Mentioned

Living Image

Related Concepts

Related Feeds

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.

Cancer Epigenetics Chromatin Complexes (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin complexes and their role in cancer epigenetics.

Cancer Epigenetics and Chromatin (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin and its role in cancer epigenetics please follow this feed to learn more.

Cancer Epigenetics & Methyl-CpG (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. Here is the latest research on cancer epigenetics and methyl-CpG binding proteins including ZBTB38.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

Cancer Epigenetics

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. Here is the latest research on cancer epigenetics.

Cell Signaling & Cancer Epigenetics (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. This feed covers the latest research on signaling and epigenetics in cell growth and cancer.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Related Papers

Translational Research : the Journal of Laboratory and Clinical Medicine
Kristen M Meldi, Maria E Figueroa
[Rinshō ketsueki] The Japanese journal of clinical hematology
H Hirai
© 2022 Meta ULC. All rights reserved