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Open AccessReview

Epigenetic Modifiers in Myeloid Malignancies: The Role of Histone Deacetylase Inhibitors

Department of Medicine, Huddinge, Karolinska Institutet, and Hematology Center, and Karolinska University Hospital, S-141 86 Stockholm, Sweden
Int. J. Mol. Sci. 2018, 19(10), 3091; https://doi.org/10.3390/ijms19103091
Received: 18 August 2018 / Revised: 1 October 2018 / Accepted: 5 October 2018 / Published: 9 October 2018
(This article belongs to the Special Issue Histone Deacetylase Inhibitors in Health and Disease)
Myeloid hematological malignancies are clonal bone marrow neoplasms, comprising of acute myeloid leukemia (AML), the myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), the myeloproliferative neoplasms (MPN) and systemic mastocytosis (SM). The field of epigenetic regulation of normal and malignant hematopoiesis is rapidly growing. In recent years, heterozygous somatic mutations in genes encoding epigenetic regulators have been found in all subtypes of myeloid malignancies, supporting the rationale for treatment with epigenetic modifiers. Histone deacetylase inhibitors (HDACi) are epigenetic modifiers that, in vitro, have been shown to induce growth arrest, apoptotic or autophagic cell death, and terminal differentiation of myeloid tumor cells. These effects were observed both at the bulk tumor level and in the most immature CD34+38 cell compartments containing the leukemic stem cells. Thus, there is a strong rationale supporting HDACi therapy in myeloid malignancies. However, despite initial promising results in phase I trials, HDACi in monotherapy as well as in combination with other drugs, have failed to improve responses or survival. This review provides an overview of the rationale for HDACi in myeloid malignancies, clinical results and speculations on why clinical trials have thus far not met the expectations, and how this may be improved in the future. View Full-Text
Keywords: myelodysplastic syndromes; acute myeloid leukemia; chronic myelomonocytic leukemia; systemic mastocytosis; treatment; myeloid mutations myelodysplastic syndromes; acute myeloid leukemia; chronic myelomonocytic leukemia; systemic mastocytosis; treatment; myeloid mutations
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MDPI and ACS Style

Ungerstedt, J.S. Epigenetic Modifiers in Myeloid Malignancies: The Role of Histone Deacetylase Inhibitors. Int. J. Mol. Sci. 2018, 19, 3091. https://doi.org/10.3390/ijms19103091

AMA Style

Ungerstedt JS. Epigenetic Modifiers in Myeloid Malignancies: The Role of Histone Deacetylase Inhibitors. International Journal of Molecular Sciences. 2018; 19(10):3091. https://doi.org/10.3390/ijms19103091

Chicago/Turabian Style

Ungerstedt, Johanna S. 2018. "Epigenetic Modifiers in Myeloid Malignancies: The Role of Histone Deacetylase Inhibitors" Int. J. Mol. Sci. 19, no. 10: 3091. https://doi.org/10.3390/ijms19103091

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