title: Induction of cancer testis antigen expression in circulating acute myeloid leukemia blasts following hypomethylating agent monotherapy.
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.
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Pragya
authors.initials: P
authors.lastname: Srivastava
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Paluch
authors.affiliation: Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Junko
authors.initials: J
authors.lastname: Matsuzaki
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Smitha R
authors.initials: SR
authors.lastname: James
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Golda
authors.initials: G
authors.lastname: Collamat-Lai
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of Freiburg, Medical Center, Freiburg, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Blagitko-Dorfs
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Laurie Ann
authors.initials: LA
authors.lastname: Ford
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Rafeh
authors.initials: R
authors.lastname: Naqash
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of Freiburg, Medical Center, Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.affiliation: Eppley Institute for Cancer Research, Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Karpf
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.|Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Nemeth
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.|Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA.|Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Griffiths
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077209:Decitabine; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C104948:CTAG1B protein, human; D008565:Membrane Proteins; D000077209:Decitabine; D001374:Azacitidine
keywords: NY-ESO-1; acute myeloid leukemia; cancer testis antigen; decitabine; immunotherapy