The Clinical Value of Decitabine Monotherapy in Patients with Acute Myeloid Leukemia

Lübbert, Michael; Wierzbowska, Agnieszka; Ossenkoppele, Gert J.

doi:10.1007/s12325-021-01948-8

Cited by 8 publications

(5 citation statements)

References 56 publications

(74 reference statements)

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“…Furthermore, we could identify tneopeptide-specific CD4 + memory T cells in an AML patient who received in vivo DAC treatment. These findings could explain the observed benefit of DAC therapy in several clinical trials [39][40][41] . However, this patient also received HDAC inhibitor Valproic acid (VPA) in addition to DAC.…”

Section: Discussionmentioning

confidence: 72%

DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts

Goyal,

Bauer,

Hey

et al. 2023

Nat Commun

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Immunotherapies targeting cancer-specific neoantigens have revolutionized the treatment of cancer patients. Recent evidence suggests that epigenetic therapies synergize with immunotherapies, mediated by the de-repression of endogenous retroviral element (ERV)-encoded promoters, and the initiation of transcription. Here, we use deep RNA sequencing from cancer cell lines treated with DNA methyltransferase inhibitor (DNMTi) and/or Histone deacetylase inhibitor (HDACi), to assemble a de novo transcriptome and identify several thousand ERV-derived, treatment-induced novel polyadenylated transcripts (TINPATs). Using immunopeptidomics, we demonstrate the human leukocyte antigen (HLA) presentation of 45 spectra-validated treatment-induced neopeptides (t-neopeptides) arising from TINPATs. We illustrate the potential of the identified t-neopeptides to elicit a T-cell response to effectively target cancer cells. We further verify the presence of t-neopeptides in AML patient samples after in vivo treatment with the DNMT inhibitor Decitabine. Our findings highlight the potential of ERV-derived neoantigens in epigenetic and immune therapies.

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Section: Discussionmentioning

confidence: 72%

DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts

Goyal,

Bauer,

Hey

et al. 2023

Nat Commun

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“…Since MCC is considered an aggressive and deadly tumor, there is an urgent need to identify novel effective therapies for its management. As the malignant behaviour of MCC cells can be reverted with iHDACs ( 17 , 69 , 71 , 72 , 77 ), combination multidrug therapies with hypomethylating agents should be considered ( 45 , 107 , 108 ), as has successfully been demonstrated in treating other tumors ( 109 – 111 ). We therefore recommend further rigorous preclinical/clinical studies in this direction ( 112 ).…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

The Role of Histone Post-Translational Modifications in Merkel Cell Carcinoma

et al. 2022

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Merkel Cell Carcinoma (MCC) is a rare but highly aggressive form of non–melanoma skin cancer whose 5-year survival rate is 63%. Merkel cell polyomavirus (MCPyV), a small DNA tumor virus, is the etiological agent of MCC. Although representing a small proportion of MCC cases, MCPyV-negative MCCs have also been identified. The role of epigenetic mechanisms, including histone post-translational modifications (PTMs) in MCC, have been only partially determined. This review aims to describe the most recent progress on PTMs and their regulative factors in the context of MCC onset/development, providing an overview of current findings on both MCC subtypes. An outline of current knowledge on the potential employment of PTMs and related factors as diagnostic and prognostic markers, as well as novel treatment strategies targeting the reversibility of PTMs for MCC therapy is provided. Recent research shows that PTMs are emerging as important epigenetic players involved in MCC onset/development, and therefore may show a potential clinical significance. Deeper and integrated knowledge of currently known PTM dysregulations is of paramount importance in order to understand the molecular basis of MCC and improve the diagnosis, prognosis, and therapeutic options for this deadly tumor.

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“…1 Acute myeloid leukemia results in impaired blood cell production and bone marrow failure. 2 If left untreated, patients with this disorder can die in a few weeks due to increased susceptibility to blood infections or uncontrolled blood loss caused by excessive bleeding. 3 Acute leukemia is generally classified as either acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), according to its distinctive morphology, prognosis and preferred treatment protocols to differentiate them.…”

Section: Introductionmentioning

confidence: 99%

Tumor suppressor miR-520a inhibits cell growth by negatively regulating PI3K/AKT signaling pathway in acute myeloid leukemia

Xiao,

Wan,

Tian

et al. 2023

Adv Clin Exp Med

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The Clinical Value of Decitabine Monotherapy in Patients with Acute Myeloid Leukemia

Cited by 8 publications

References 56 publications

DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts

DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts

The Role of Histone Post-Translational Modifications in Merkel Cell Carcinoma

Tumor suppressor miR-520a inhibits cell growth by negatively regulating PI3K/AKT signaling pathway in acute myeloid leukemia

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