Induction of cancer testis antigen expression in circulating acute myeloid leukemia blasts following hypomethylating agent monotherapy

Oncotarget
Pragya SrivastavaElizabeth A Griffiths

Abstract

Cancer testis antigens (CTAs) are promising cancer associated antigens in solid tumors, but in acute myeloid leukemia, dense promoter methylation silences their expression. Leukemia cell lines exposed to HMAs induce expression of CTAs. We hypothesized that AML patients treated with standard of care decitabine (20mg/m2 per day for 10 days) would demonstrate induced expression of CTAs. Peripheral blood blasts serially isolated from AML patients treated with decitabine were evaluated for CTA gene expression and demethylation. Induction of NY-ESO-1 and MAGEA3/A6, were observed following decitabine. Re-expression of NY-ESO-1 and MAGEA3/A6 was associated with both promoter specific and global (LINE-1) hypomethylation. NY-ESO-1 and MAGEA3/A6 mRNA levels were increased irrespective of clinical response, suggesting that these antigens might be applicable even in patients who are not responsive to HMA therapy. Circulating blasts harvested after decitabine demonstrate induced NY-ESO-1 expression sufficient to activate NY-ESO-1 specific CD8+ T-cells. Induction of CTA expression sufficient for recognition by T-cells occurs in AML patients receiving decitabine. Vaccination against NY-ESO-1 in this patient population is feasible.

References

May 1, 1990·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·B D ChesonM J Keating
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Aug 3, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kazuhiko NakagawaEiichi Nakayama
May 12, 2006·Molecular Cancer Research : MCR·Frank WischnewskiHeidi Schwarzenbach
May 19, 2006·Cancer Research·Allen S YangJean-Pierre J Issa
Nov 30, 2007·Cancer Immunology, Immunotherapy : CII·A Nazmul H KhanThomas B Tomasi
Jan 22, 2008·Journal of Cellular Physiology·Luca SigalottiMichele Maio
Jun 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anna Woloszynska-ReadAdam R Karpf
Feb 8, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anna Woloszynska-ReadAdam R Karpf
Sep 8, 2011·American Journal of Hematology·Djordje AtanackovicNicolaus Kröger
Mar 16, 2012·The New England Journal of Medicine·Jay P PatelRoss L Levine
Mar 29, 2012·Proceedings of the National Academy of Sciences of the United States of America·Kunle OdunsiElke Jäger
Jul 4, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emily Corse, James P Allison
Aug 24, 2012·Carcinogenesis·Pragya SrivastavaDhyan Chandra
Nov 10, 2012·Cancer Immunology, Immunotherapy : CII·Sandra CoralMichele Maio
Nov 16, 2012·International Journal of Cancer. Journal International Du Cancer·Vincenzo RussoMarco Bregni
May 30, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Johan VansteenkisteVincent G Brichard
Jul 11, 2013·Epigenetics : Official Journal of the DNA Methylation Society·Smitha R JamesAdam R Karpf
Jul 16, 2013·Journal of the National Cancer Institute·Patrizia LeoneVito Racanelli
Feb 19, 2014·Cancer Immunology Research·Kunle OdunsiAdam R Karpf
Dec 30, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Paul F RobbinsSteven A Rosenberg
Mar 21, 2015·Epigenetics : Official Journal of the DNA Methylation Society·Pragya SrivastavaElizabeth A Griffiths

❮ Previous
Next ❯

Citations

Jul 1, 2017·Targeted Oncology·Maximilian StahlAmer M Zeidan
Jan 11, 2018·British Journal of Haematology·Willemijn HoboHarry Dolstra
Jul 7, 2017·Leukemia & Lymphoma·Prajwal BodduNaval Daver
May 1, 2019·Molecular and Cellular Biology·Zachary R GallegosAngelique W Whitehurst
Nov 30, 2019·British Journal of Haematology·A John Barrett
Jul 11, 2018·Seminars in Immunopathology·Morten Orebo Holmström, Hans Carl Hasselbalch
Jun 12, 2020·Molecular Oncology·Pedro BlecuaManel Esteller
Dec 2, 2018·Journal of Oncology·Maiko Matsushita, Mai Kawaguchi
Mar 25, 2019·Current Oncology Reports·Maximilian Stahl, Aaron D Goldberg
Feb 6, 2019·Therapeutic Advances in Hematology·Jan Philipp BewersdorfAmer M Zeidan
May 22, 2020·Frontiers in Oncology·Sherly Mardiana, Saar Gill
Jul 2, 2020·Cells·Lukas M Braun, Robert Zeiser
Oct 18, 2018·Frontiers in Immunology·Uffe KlausenMads Hald Andersen
Apr 23, 2020·Current Cancer Drug Targets·Rohit ThummalapalliJoshua F Zeidner
Mar 4, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniela MateiGini F Fleming
Sep 28, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elizabeth A GriffithsMichael J Nemeth
Dec 30, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ephraim Joseph Fuchs
May 14, 2020·Blood Reviews·Rajat Bansal, Ran Reshef
Sep 9, 2019·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Yi-Geng CaoMing-Zhe Han
Nov 27, 2020·Therapeutic Advances in Hematology·Jan Philipp BewersdorfThomas Prebet
Feb 12, 2021·Frontiers in Immunology·Heather F JonesDavid A Scheinberg
Feb 21, 2021·Molecular Cell·Helen Loo YauDaniel D De Carvalho
May 5, 2021·Human Vaccines & Immunotherapeutics·Katherine Linder, Premal Lulla
May 7, 2021·Immunotherapy·Ming WuYu-Hua Li

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
MDS
flow cytometry
PMA
Assay

Software Mentioned

GraphPad Prism
FlowJo

Related Concepts

Related Feeds

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.

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.

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.