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Introduction: Acute myeloid leukemia (AML) patients may receive hypomethylating agents (HMAs) such as decitabine (DAC) as part of their treatment. Not all patients respond to this therapy, and if they do the clinical response may occur only after 3 to 6 courses of treatment. Hence, early biomarkers predicting response would be very useful. Methods: We retrospectively analyzed a cohort of 22 AML patients who were treated with DAC. Histology of the bone marrow biopsy, pathogenic mutations and methylation status were related to the treatment response. Results: In 8/22 (36%) patients, an erythroid dominant response (EDR) pattern, defined as a ratio of myeloid cells/erythroid cells < 1, was observed. In the remaining 14 cases a myeloid predominance was preserved during treatment. No difference in the hypomethylating effect of DAC treatment was observed in patients with and without EDR, as global 5-methylcytosine levels dropped similarly in both groups. Mutational analysis by NGS using a panel of commonly mutated genes in AML, showed that patients with an early EDR harbored on average less mutations, with U2AF1 mutations occurring more frequently, whereas RUNX1 mutations were underrepresented compared to non-EDR cases. Interestingly, the development of an EDR correlated with complete remission (7/8 cases with an EDR versus only 2/14 cases without an EDR). Conclusion: We conclude that early histological bone marrow examination for the development of an EDR may be helpful to predict response in AML patients during treatment with DAC.

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