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The role of EVI1 gene quantification in AML patients with 11q23/MLL rearrangement after allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 56, pages 470–480 (2021)Cite this article

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Abstract

It remains unclear about the role of the EVI1 gene in AML patients with 11q23/MLL rearrangement (MLL-r AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We analyzed the clinical value of EVI1 gene quantification in 96 MLL-r AML patients. High EVI1 expression was found in 73% (70/96) of MLL-r AML patients, and EVI1-high MLL-r AML patients were characterized by high WBC counts (P = 0.046) and low platelet counts (P < 0.001) and commonly had t(6;11) (P = 0.032). In addition, a significant difference was observed in the SETD2 gene mutation between the EVI1 high and low groups (0% vs. 50%, P < 0.001). EVI1-high MLL-r AML patients had worse 2-year OS (49.8% vs. 79.7%, P = 0.01) and 2-year PFS (40.2% vs. 68.1%, P = 0.014) than EVI1-low patients. In 57 MLL-r AML patients undergoing allo-HSCT, poorer 2-year PFS (48.6% vs. 72.4%, P = 0.039) and higher CIR (33.2% vs. 11.1%, P = 0.035) were observed in the EVI1-high patients. Multivariate analysis revealed that pre-EVI1+ was the sole independent factor of high CIR (P = 0.035, HR = 4.97, 95% CI: 1.12–22.04). EVI1+ at 100 days post allo-HSCT was associated with a significantly higher 2-year CIR (P = 0.017). The quantification of the EVI1 gene could be used as an additional marker for early predicting relapse in allo-HSCT MLL-r AML patients.

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Fig. 1: Mutations in 32 EVI1-high patients and in 12 EVI1-low patients detected by next-generation sequencing.
Fig. 2: Survival outcome for 96 MLL-r AML patients.
Fig. 3: Survival outcome for 57 MLL-r AML patients undergoing allo-HSCT according to EVI1 levels.
Fig. 4: Survival outcome for 57 MLL-r AML patients undergoing allo-HSCT according to pre-EVI1 status.
Fig. 5: EVI1+ at day 100 was associated with a significantly higher 2-year CIR.

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Acknowledgements

This work has been supported by grants from the National Natural Science Foundation of China (81730003, 81870120), the Natural Science Foundation of Jiangsu Province (BK20171205), the Social Development Project of Jiangsu Province (BE2019655), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the National Key Research and Development Program (2017ZX09304021, 2017YFA0104500, 2019YFC0840604). All the samples were from Jiangsu Biobank of Clinical Resources.

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  1. These authors contributed equally: Shuhui Jiang, Yi Fan, Yanglan Fang

Authors and Affiliations

  1. National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China

    Shuhui Jiang, Yi Fan, Yanglan Fang, Chang Hou, Jia Chen, Jiannong Cen, Huiying Qiu, Suning Chen, Yang Xu & Depei Wu

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

    Shuhui Jiang, Yi Fan, Yanglan Fang, Chang Hou, Jia Chen, Jiannong Cen, Huiying Qiu, Suning Chen, Yang Xu & Depei Wu

  3. Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou, China

    Shuhui Jiang, Yi Fan, Yanglan Fang, Chang Hou, Jia Chen, Jiannong Cen, Huiying Qiu, Suning Chen, Yang Xu & Depei Wu

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Contributions

DW and YX contributed to the conception of the study and paper revision. SJ, YFan, and YFang contributed to collecting and performing the data analysis and preparing the paper. CH and JChen helped collect and perform data analysis and prepare the paper. JCen, HQ, and SC contributed to the data analysis and paper revision.

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Correspondence to Yang Xu or Depei Wu.

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Jiang, S., Fan, Y., Fang, Y. et al. The role of EVI1 gene quantification in AML patients with 11q23/MLL rearrangement after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 56, 470–480 (2021). https://doi.org/10.1038/s41409-020-01048-1

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