Epigenetic Modifications in Acute Myeloid Leukemia: Prognosis, Treatment, and Heterogeneity

doi:10.3389/fgene.2019.00133

Review

. 2019 Mar 1:10:133.

doi: 10.3389/fgene.2019.00133. eCollection 2019.

Epigenetic Modifications in Acute Myeloid Leukemia: Prognosis, Treatment, and Heterogeneity

Samantha L Goldman^{1

2

3}, Ciaran Hassan^{1

2

4}, Mihir Khunte^{1

4}, Arielle Soldatenko^{1

4}, Yunji Jong^{1

4}, Ebrahim Afshinnekoo^{1

2

5}, Christopher E Mason^{1

2

5

6}

Affiliations

¹ Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United States.
² The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, United States.
³ University of Maryland, College Park, MD, United States.
⁴ Yale College, New Haven, CT, United States.
⁵ The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, United States.
⁶ The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, United States.

PMID: 30881380
PMCID: PMC6405641
DOI: 10.3389/fgene.2019.00133

Review

Epigenetic Modifications in Acute Myeloid Leukemia: Prognosis, Treatment, and Heterogeneity

Samantha L Goldman et al. Front Genet. 2019.

. 2019 Mar 1:10:133.

doi: 10.3389/fgene.2019.00133. eCollection 2019.

Authors

Samantha L Goldman^{1

2

3}, Ciaran Hassan^{1

2

4}, Mihir Khunte^{1

4}, Arielle Soldatenko^{1

4}, Yunji Jong^{1

4}, Ebrahim Afshinnekoo^{1

2

5}, Christopher E Mason^{1

2

5

6}

Affiliations

¹ Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, United States.
² The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, United States.
³ University of Maryland, College Park, MD, United States.
⁴ Yale College, New Haven, CT, United States.
⁵ The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, United States.
⁶ The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, United States.

PMID: 30881380
PMCID: PMC6405641
DOI: 10.3389/fgene.2019.00133

Abstract

Leukemia, specifically acute myeloid leukemia (AML), is a common malignancy that can be differentiated into multiple subtypes based on leukemogenic history and etiology. Although genetic aberrations, particularly cytogenetic abnormalities and mutations in known oncogenes, play an integral role in AML development, epigenetic processes have been shown as a significant and sometimes independent dynamic in AML pathophysiology. Here, we summarize how tumors evolve and describe AML through an epigenetic lens, including discussions on recent discoveries that include prognostics from epialleles, changes in RNA function for hematopoietic stem cells and the epitranscriptome, and novel epigenetic treatment options. We further describe the limitations of treatment in the context of the high degree of heterogeneity that characterizes acute myeloid leukemia.

Keywords: AML; acute myeloid leukemia; epialleles; epigenetics; heterogeneity.

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References

1. Afshinnekoo A., Mason C. E. (2016). Epigenetic therapy in a new era of medicine: creating and integrating molecular profiles of patients. Ann. Transl. Med. 4:436. 10.21037/atm.2016.11.19, PMID: - DOI - PMC - PubMed
1. Agirre X., Meydan C., Jiang Y., Garate L., Doane A. S., Li Z., et al. (2018). Long non-coding RNAs discriminate the stages and gene regulatory states of human humoral immune response. 10.1038/s41467-019-08679-z - DOI - PMC - PubMed
1. Agrawal S., Hofmann W. -K., Tidow N., Ehrich M., Boom D. v. d., Koschmieder S., et al. . (2007). The C/EBP tumor suppressor is silenced by hypermethylation in acute myeloid leukemia. Blood 109, 3895–3905. 10.1182/blood-2006-08-040147, PMID: - DOI - PubMed
1. Allis C. D., Jenuwein T. (2016). The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 17, 487–500. 10.1038/nrg.2016.59, PMID: - DOI - PubMed
1. Asou N. (2003). The role of a Runt domain transcription factor AML1/RUNX1 in leukemogenesis and its clinical implications. Crit. Rev. Oncol. Hematol. 45, 129–150. 10.1016/S1040-8428(02)00003-3, PMID: - DOI - PubMed

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[1] Afshinnekoo A., Mason C. E. (2016). Epigenetic therapy in a new era of medicine: creating and integrating molecular profiles of patients. Ann. Transl. Med. 4:436. 10.21037/atm.2016.11.19, PMID: - DOI - PMC - PubMed

[2] Afshinnekoo A., Mason C. E. (2016). Epigenetic therapy in a new era of medicine: creating and integrating molecular profiles of patients. Ann. Transl. Med. 4:436. 10.21037/atm.2016.11.19, PMID: - DOI - PMC - PubMed

[3] Agirre X., Meydan C., Jiang Y., Garate L., Doane A. S., Li Z., et al. (2018). Long non-coding RNAs discriminate the stages and gene regulatory states of human humoral immune response. 10.1038/s41467-019-08679-z - DOI - PMC - PubMed

[4] Agirre X., Meydan C., Jiang Y., Garate L., Doane A. S., Li Z., et al. (2018). Long non-coding RNAs discriminate the stages and gene regulatory states of human humoral immune response. 10.1038/s41467-019-08679-z - DOI - PMC - PubMed

[5] Agrawal S., Hofmann W. -K., Tidow N., Ehrich M., Boom D. v. d., Koschmieder S., et al. . (2007). The C/EBP tumor suppressor is silenced by hypermethylation in acute myeloid leukemia. Blood 109, 3895–3905. 10.1182/blood-2006-08-040147, PMID: - DOI - PubMed

[6] Agrawal S., Hofmann W. -K., Tidow N., Ehrich M., Boom D. v. d., Koschmieder S., et al. . (2007). The C/EBP tumor suppressor is silenced by hypermethylation in acute myeloid leukemia. Blood 109, 3895–3905. 10.1182/blood-2006-08-040147, PMID: - DOI - PubMed

[7] Allis C. D., Jenuwein T. (2016). The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 17, 487–500. 10.1038/nrg.2016.59, PMID: - DOI - PubMed

[8] Allis C. D., Jenuwein T. (2016). The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 17, 487–500. 10.1038/nrg.2016.59, PMID: - DOI - PubMed

[9] Asou N. (2003). The role of a Runt domain transcription factor AML1/RUNX1 in leukemogenesis and its clinical implications. Crit. Rev. Oncol. Hematol. 45, 129–150. 10.1016/S1040-8428(02)00003-3, PMID: - DOI - PubMed

[10] Asou N. (2003). The role of a Runt domain transcription factor AML1/RUNX1 in leukemogenesis and its clinical implications. Crit. Rev. Oncol. Hematol. 45, 129–150. 10.1016/S1040-8428(02)00003-3, PMID: - DOI - PubMed

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Epigenetic Modifications in Acute Myeloid Leukemia: Prognosis, Treatment, and Heterogeneity

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Epigenetic Modifications in Acute Myeloid Leukemia: Prognosis, Treatment, and Heterogeneity

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