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High frequency of RUNX1 mutation in myelodysplastic syndrome patients with whole-arm translocation of der(1;7)(q10;p10)

Leukemia volume 31, pages 2257–2260 (2017)Cite this article

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Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematologic malignancies.1 Chromosomal abnormalities are detected in about half of MDS cases and are recognized as the most important prognostic parameters.2, 3, 4 der(1;7)(q10;p10) is a nonrandom and relatively rare acquired chromosomal abnormality in MDS, resulting in trisomy 1q and monosomy 7q.5 As Geraedts et al. firstly reported the der(1;7)(q10;p10) in 1980, nearly 300 cases have been reported so far.5, 6, 7, 8, 9, 10, 11 The der(1;7)(q10;p10) commonly occurred in myeloid malignancies and was reported at frequencies of 1–3% in MDS, 1–2% in acute myeloid leukemia, and 1% in myeloproliferative neoplasm. There is some controversy over the prognosis of the der(1;7)(q10;p10). Sanada et al. reported a better outcome of der(1;7)(q10;p10) compared with -7/del(7q) cases in a retrospective study including 77 patients with MDS,9 while there was no statistical difference in overall survival (OS) between der(1;7)(q10;p10) and -7/del(7q) in several other studies.10, 11 In addition, Westman et al. identified isocitrate dehydrogenases 1 and 2 mutations in 4 out of 11 MDS or acute myeloid leukemia patients with der(1;7)(q10;p10).7 However, given the dearth of reports hitherto, the clinical and laboratory features of patients with der(1;7)(q10;p10) remain largely undefined. In the present study, we performed targeted next-generation sequencing (NGS) on 22 cases with der(1;7)(q10;p10) to decipher the somatic mutation spectrum of this entity.

From January 1984 to December 2015, a total of 70 der(1;7)(q10;p10) patients were included. The study was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University and informed consent was obtained from all subjects. A strong male predominance was showed in patients with der(1;7)(q10;p10): 84.3% of them were male (59/70). The median age was 56 years (range, 16–82 years). Based on review of the patient records, these patients were further classified as follows: 50 (71.4%) MDS, 15 (21.4%) acute myeloid leukemia, 3 (4.3%) multiple myeloma, 1 chronic myeloid leukemia and 1 hypereosinophilic syndrome. These 50 MDS patients with der(1;7)(q10;p10) were identified from 1934 MDS patients with karyotypic data available, thus the frequency of der(1;7)(q10;p10) in MDS is 2.6% (50/1934) in our center. Among 50 MDS patients with der(1;7)(q10;p10), most of them were male (82.0%, 41/50) and the median age was 60 years (range, 16–82 years). Main patient characteristics are summarized in Table 1 and Supplementary Table 1.

Table 1 Clinical and cytogenetic characteristics of MDS study cohort
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Acknowledgements

This work was supported by grants from the Priority Academic Program Development of Jiangsu Higher Education Institutions, the Natural Science Foundation of China (81570139, 81370626, 81070416, 81300424, 81400112), the national key research and development program, 2016YFC0902800), the Innovation Capability Development Project of Jiangsu Province (BM2015004), and Jiangsu Province Natural Science Fund (BE2015639).

Author contributions

SC and AS were the principal investigators. TZ, YX, JP, QW, LW and DP performed most of the experiments. HL performed structural model of RUNX1. SC and AS wrote the manuscript.

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  1. T Zhang and Y Xu: These authors contributed equally to this work.

Authors and Affiliations

  1. Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, the First Affiliated Hospital of Soochow University, Suzhou, China

    T Zhang, Y Xu, J Pan, Q Wang, L Wen, D Wu, A Sun & S Chen

  2. Department of Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA

    H Li

  3. Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China

    D Wu & S Chen

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  1. T Zhang
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Zhang, T., Xu, Y., Pan, J. et al. High frequency of RUNX1 mutation in myelodysplastic syndrome patients with whole-arm translocation of der(1;7)(q10;p10). Leukemia 31, 2257–2260 (2017). https://doi.org/10.1038/leu.2017.228

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