International Journal of Medical Sciences

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16 January 2019

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Int J Med Sci 2015; 12(1):17-22. doi:10.7150/ijms.10144

Research Paper

Quantitative Detection of Circulating Nucleophosmin Mutations DNA in the Plasma of Patients with Acute Myeloid Leukemia

Jing Quan1, Yu-jie Gao2, Zai-lin Yang3, Hui Chen4, Jing-rong Xian1, Shuai-shuai Zhang1, Qin Zou1, Ling Zhang1✉

1. Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Yixueyuan Road, Chongqing 400016, P.R.China.
2. Department of Laboratory Medicine, Yantai Yuhuangding Hospital, Yantai 264000, P.R.China.
3. Center for Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R.China.
4. Department of Laboratory Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R.China.


Objective: The aim of this study was to quantify the copies of circulating nucleophosmin (NPM) mutations DNA in the plasma of patients with acute myeloid leukemia (AML) and to explore the association of circulating NPM mutation levels with clinical characteristics.

Design and Methods: The presence of NPM mutations in 100 Chinese patients newly diagnosed with AML were identified by RT-PCR and sequencing analysis. Copies of circulating NPM mutation A (NPM mut.A) DNA in the plasma of mutation-positive cases were quantified by real-time quantitative PCR (qRT-PCR). Furthermore, the association of circulating NPM mutation levels and clinical characteristics was analyzed.

Results: NPM mutations were identified in 37 of the 100 patients and all cases were NPM mut.A. The circulating NPM mut.A levels ranged from 0.35×108 copies/ml to 6.0×108 copies/ml in the 37 mutation-positive cases. The medium and quartile M (P25, P75) of the circulating NPM mut.A levels in patients classified as M2, M4 and M5 morphological subtypes were 1.35×108 (0.76×108, 1.91×108) copies/ml, 1.81×108 (1.47×108, 2.2×108) copies/ml and 2.50×108 (2.42×108, 3.05×108) copies/ml, respectively. Circulating NPM mut.A levels were significantly higher in patients with the M5 subtype of AML compared to patients with the M2 and M4 subtypes (p=0.000, p=0.046). In addition, circulating NPM mut.A copies were significantly associated with a higher white blood cell count, platelet count and bone marrow blast percentage (p<0.05).

Conclusion: Our results suggest that circulating NPM mutations DNA assay serves as a complementary to the routine investigative protocol of NPM-mutated leukemia.

Keywords: nucleophosmin, mutation, acute myeloid leukemia, circulating DNA, real-time quantitative polymerase chain reaction.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
How to cite this article:
Quan J, Gao Yj, Yang Zl, Chen H, Xian Jr, Zhang Ss, Zou Q, Zhang L. Quantitative Detection of Circulating Nucleophosmin Mutations DNA in the Plasma of Patients with Acute Myeloid Leukemia. Int J Med Sci 2015; 12(1):17-22. doi:10.7150/ijms.10144. Available from