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The predictive value of minimal residual disease when facing the inconsistent results detected by real-time quantitative PCR and flow cytometry in NPM1-mutated acute myeloid leukemia

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Abstract

For acute myeloid leukemia (AML) with nucleophosmin 1 mutation (NPM1m), multiparameter flow cytometry (FCM) and real-time quantitative polymerase chain reaction (RQ-PCR) are used to monitor minimal residual disease (MRD). However, the results of the two methods are sometimes inconsistent. This study was designed to analyze how to address the discordant results of FCM and RQ-PCR in AML patients undergoing chemotherapy, especially when positive FCM (FCM+) and negative NPM1m (NPM1m−) results are detected in the same sample. Our study included 93 AML patients with NPM1m positive (NPM1m+) who received chemotherapy but did not undergo hematopoietic stem cell transplantation. We monitored NPM1m and leukemia-associated immunophenotypes (LAIPs) by RQ-PCR and FCM, respectively, to assess MRD after each chemotherapy course. After each course of chemotherapy, all patients were classified into four groups based on the results of FCM and RQ-PCR: both negative (group 1, FCM−NPM1m−), single positive (group 2, FCM−NPM1m+; group 3, FCM+NPM1m−), or both positive (group 4, FCM+NPM1m+). The results showed that there was not a significant difference in the 2-year cumulative incidence of relapse (CIR) after each course of chemotherapy between group 2 and group 3. Furthermore, patients in groups 2 and 3 had a lower 2-year CIR than those in group 4 and a significantly higher 2-year CIR than those in group 1 after the first two courses. The patients in group 4 had a significantly higher 2-year CIR than those in group 1 after the first two courses. These results suggested that in the MRD monitoring process of AML patients, when the results of FCM and RQ-PCR are inconsistent (especially when FCM is positive and NPM1m is negative), these single-positive results still have predictive significance for relapse.

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Acknowledgments

The authors thank American Journal Experts (www.journalexperts.com) for their assistance in editing this manuscript. The work was supported by the National Key Research and Development Program of China (2017YFA0104500), the National Natural Science Foundation of China (grant no. 81670175, grant no. 81870137), and the Innovative Research Groups of the National Natural Science Foundation of China (grant no. 81621001).

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Authors and Affiliations

  1. National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Peking University People’s Hospital, No. 11 South Street of Xizhimen, Xicheng District, Beijing, 100044, China

    Meng-Ge Gao, Guo-Rui Ruan, Ying-Jun Chang, Yan-Rong Liu, Ya-Zhen Qin, Qian Jiang, Hao Jiang, Xiao-Jun Huang & Xiao-Su Zhao

  2. Collaborative Innovation Center of Hematology, Peking University, Beijing, China

    Ying-Jun Chang, Xiao-Jun Huang & Xiao-Su Zhao

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  1. Meng-Ge Gao
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Correspondence to Xiao-Su Zhao.

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Gao, MG., Ruan, GR., Chang, YJ. et al. The predictive value of minimal residual disease when facing the inconsistent results detected by real-time quantitative PCR and flow cytometry in NPM1-mutated acute myeloid leukemia. Ann Hematol 99, 73–82 (2020). https://doi.org/10.1007/s00277-019-03861-1

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