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Predictors of clinical responses to hypomethylating agents in acute myeloid leukemia or myelodysplastic syndromes

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Abstract

Azacitidine and decitabine, two hypomethylating agents, are known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who cannot endure intensive cytotoxic chemotherapy or are not eligible for transplantation. However, the treatment response rate is low. The molecular mechanisms underlying the resistance to demethylation therapy are unclear. Though a wide range of predictors of treatment response have been investigated, no consensus has been reached. It is imperative to identify certain parameters that can help distinguish between patients who will obtain a favorable outcome from demethylation therapy and those who will not. Here, we describe currently researched potential predictors based on clinical characteristics, DNA methylation, gene mutation, gene expression, microRNAs, and protein expression. Although these parameters are not currently used in clinical practice, this review provides new sights into available clinical and experimental research. Moreover, this paper provides useful information on AML/MDS management.

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Funding

This study was funded by the National Natural Science Foundation of China (grant nos. 8167016, 81370635, 81170518, 81270611, 81570137, 81470010, and 81400135), Capital Medical Development Scientific Research Fund (grant no. SF2001-5001-07), Beijing Natural Science Foundation (grant no. 7151009), National Public Health Grant Research Foundation (grant no. 201202017), The Capital of the Public Health Project (grant no. Z111107067311070), and Technology Innovation Nursery Foundation (grant no. 13KMM01). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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  1. Hong Wang and Yan Li contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology and BMT Center, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China

    Hong Wang, Yan Li, Na Lv, Yonghui Li, Lili Wang & Li Yu

  2. Medical School of Nankai University, 94 Weijin Road, Tianjin, 300071, China

    Hong Wang

  3. Department of Hematology, Hainan Branch of Chinese PLA General Hospital, Sanya, 572013, Hainan Province, China

    Yan Li

  4. Department of Hematology, Carson International Cancer Center, General Hospital of Shenzhen University, 1098 Xueyuan Ave, Shenzhen, 518060, China

    Na Lv & Li Yu

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  1. Hong Wang
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Wang, H., Li, Y., Lv, N. et al. Predictors of clinical responses to hypomethylating agents in acute myeloid leukemia or myelodysplastic syndromes. Ann Hematol 97, 2025–2038 (2018). https://doi.org/10.1007/s00277-018-3464-9

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  • DOI: https://doi.org/10.1007/s00277-018-3464-9

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